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1
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Semchyshyn H. Fructose-mediated AGE-RAGE axis: approaches for mild modulation. Front Nutr 2024; 11:1500375. [PMID: 39698244 PMCID: PMC11652219 DOI: 10.3389/fnut.2024.1500375] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 11/20/2024] [Indexed: 12/20/2024] Open
Abstract
Fructose is a valuable and healthy nutrient when consumed at normal levels (≤50 g/day). However, long-term consumption of excessive fructose and elevated endogenous production can have detrimental health impacts. Fructose-initiated nonenzymatic glycation (fructation) is considered as one of the most likely mechanisms leading to the generation of reactive species and the propagation of nonenzymatic processes. In the later stages of glycation, poorly degraded advanced glycation products (AGEs) are irreversibly produced and accumulated in the organism in an age- and disease-dependent manner. Fructose, along with various glycation products-especially AGEs-are present in relatively high concentrations in our daily diet. Both endogenous and exogenous AGEs exhibit a wide range of biological effects, mechanisms of which can be associated with following: (1) AGEs are efficient sources of reactive species in vivo, and therefore can propagate nonenzymatic vicious cycles and amplify glycation; and (2) AGEs contribute to upregulation of the specific receptor for AGEs (RAGE), amplifying RAGE-mediated signaling related to inflammation, metabolic disorders, chronic diseases, and aging. Therefore, downregulation of the AGE-RAGE axis appears to be a promising approach for attenuating disease conditions associated with RAGE-mediated inflammation. Importantly, RAGE is not specific only to AGEs; it can bind multiple ligands, initiating a complex RAGE signaling network that is not fully understood. Maintaining an appropriate balance between various RAGE isoforms with different functions is also crucial. In this context, mild approaches related to lifestyle-such as diet optimization, consuming functional foods, intake of probiotics, and regular moderate physical activity-are valuable due to their beneficial effects and their ability to mildly modulate the fructose-mediated AGE-RAGE axis.
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Affiliation(s)
- Halyna Semchyshyn
- Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, Ivano-Frankivsk, Ukraine
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2
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Thorne CA, Grey AC, Lim JC, Donaldson PJ. The Synergistic Effects of Polyol Pathway-Induced Oxidative and Osmotic Stress in the Aetiology of Diabetic Cataracts. Int J Mol Sci 2024; 25:9042. [PMID: 39201727 PMCID: PMC11354722 DOI: 10.3390/ijms25169042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/13/2024] [Accepted: 08/16/2024] [Indexed: 09/03/2024] Open
Abstract
Cataracts are the world's leading cause of blindness, and diabetes is the second leading risk factor for cataracts after old age. Despite this, no preventative treatment exists for cataracts. The altered metabolism of excess glucose during hyperglycaemia is known to be the underlying cause of diabetic cataractogenesis, resulting in localised disruptions to fibre cell morphology and cell swelling in the outer cortex of the lens. In rat models of diabetic cataracts, this damage has been shown to result from osmotic stress and oxidative stress due to the accumulation of intracellular sorbitol, the depletion of NADPH which is used to regenerate glutathione, and the generation of fructose metabolites via the polyol pathway. However, differences in lens physiology and the metabolism of glucose in the lenses of different species have prevented the translation of successful treatments in animal models into effective treatments in humans. Here, we review the stresses that arise from hyperglycaemic glucose metabolism and link these to the regionally distinct metabolic and physiological adaptations in the lens that are vulnerable to these stressors, highlighting the evidence that chronic oxidative stress together with osmotic stress underlies the aetiology of human diabetic cortical cataracts. With this information, we also highlight fundamental gaps in the knowledge that could help to inform new avenues of research if effective anti-diabetic cataract therapies are to be developed in the future.
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Affiliation(s)
- Courtney A. Thorne
- Department of Physiology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand; (C.A.T.); (A.C.G.); (P.J.D.)
- New Zealand National Eye Centre, University of Auckland, Auckland 1023, New Zealand
| | - Angus C. Grey
- Department of Physiology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand; (C.A.T.); (A.C.G.); (P.J.D.)
- New Zealand National Eye Centre, University of Auckland, Auckland 1023, New Zealand
| | - Julie C. Lim
- Department of Physiology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand; (C.A.T.); (A.C.G.); (P.J.D.)
- New Zealand National Eye Centre, University of Auckland, Auckland 1023, New Zealand
| | - Paul J. Donaldson
- Department of Physiology, School of Medical Sciences, University of Auckland, Auckland 1023, New Zealand; (C.A.T.); (A.C.G.); (P.J.D.)
- New Zealand National Eye Centre, University of Auckland, Auckland 1023, New Zealand
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3
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Masaki M, Shimada Y, Takeda T, Aso H, Nakamura T. Inhibitory effect of organogermanium compound 3-(trihydroxygermyl)propanoic acid on fructose-induced glycation of amino compounds. Carbohydr Res 2024; 542:109191. [PMID: 38936267 DOI: 10.1016/j.carres.2024.109191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 06/12/2024] [Accepted: 06/14/2024] [Indexed: 06/29/2024]
Abstract
3-(Trihydroxygermyl)propanoic acid (THGP), a hydrolysate of poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132, also known as repagermanium), can inhibit glycation between glucose/ribose and amino compounds. In addition, THGP may inhibit glycation by inhibiting reactions that occur after Amadori rearrangement and inducing the reversible solubilization of AGEs. In this study, we first investigated the effects and mechanisms on the glycation of fructose and amino compounds by THGP, as a greater reactivity was obtained with fructose than with glucose. Unlike other anti-glycation materials, THGP can form a complex with fructose, the initial compound of glycation. THGP also inhibited the production of AGEs and suppressed the reduction of fructose in a reaction between fructose and arginine. These results indicate that THGP forms a complex with cyclic fructose possessing a cis-diol structure at a reducing end, and that it suppresses the ring-opening of fructose and the progress of the initial glycation reaction. We next tried to evaluate the suppressive effect of glucosyl hesperidin (GHes) and THGP on the reaction of glycation between fructose and collagen. Both compounds effectively reduced the production of AGEs individually, and the combination of them led to a synergistic suppression. Therefore, through combination with other antiglycation materials, THGP may cooperatively exhibit glycation-inhibitory effects and be able to suppress the AGE production.
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Affiliation(s)
- Mika Masaki
- Asai Germanium Research Institute Co., Ltd., 3-131, Suzuranoka, Hakodate, Hokkaido, 042-0958, Japan.
| | - Yasuhiro Shimada
- Asai Germanium Research Institute Co., Ltd., 3-131, Suzuranoka, Hakodate, Hokkaido, 042-0958, Japan.
| | - Tomoya Takeda
- Asai Germanium Research Institute Co., Ltd., 3-131, Suzuranoka, Hakodate, Hokkaido, 042-0958, Japan.
| | - Hisashi Aso
- Laboratory of Animal Health Science, Graduate School of Agricultural Science, Tohoku University, 468-1, Aramaki aza, Aoba, Sendai, Miyagi, 980-8572, Japan.
| | - Takashi Nakamura
- Asai Germanium Research Institute Co., Ltd., 3-131, Suzuranoka, Hakodate, Hokkaido, 042-0958, Japan.
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4
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Shen CY, Lu CH, Cheng CF, Li KJ, Kuo YM, Wu CH, Liu CH, Hsieh SC, Tsai CY, Yu CL. Advanced Glycation End-Products Acting as Immunomodulators for Chronic Inflammation, Inflammaging and Carcinogenesis in Patients with Diabetes and Immune-Related Diseases. Biomedicines 2024; 12:1699. [PMID: 39200164 PMCID: PMC11352041 DOI: 10.3390/biomedicines12081699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2024] [Revised: 07/22/2024] [Accepted: 07/27/2024] [Indexed: 09/02/2024] Open
Abstract
Increased production of advanced glycation end products (AGEs) among reducing sugars (glucose, fructose, galactose, or ribose) and amino acids/proteins via non-enzymatic Maillard reaction can be found in lifestyle-related disease (LSRD), metabolic syndrome (MetS), and obesity and immune-related diseases. Increased serum levels of AGEs may induce aging, diabetic complications, cardiovascular diseases (CVD), neurodegenerative diseases (NDD), cancer, and inflamm-aging (inflammation with immunosenescence). The Maillard reaction can also occur among reducing sugars and lipoproteins or DNAs to alter their structure and induce immunogenicity/genotoxicity for carcinogenesis. AGEs, as danger-associated molecular pattern molecules (DAMPs), operate via binding to receptor for AGE (RAGE) or other scavenger receptors on cell surface to activate PI3K-Akt-, P38-MAPK-, ERK1/2-JNK-, and MyD88-induced NF-κB signaling pathways to mediate various pathological effects. Recently, the concept of "inflamm-aging" became more defined, and we have unveiled some interesting findings in relation to it. The purpose of the present review is to dissect the potential molecular basis of inflamm-aging in patients with diabetes and immune-mediated diseases caused by different AGEs.
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Affiliation(s)
- Chieh-Yu Shen
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, # 7 Chung-Shan South Road, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-F.C.); (K.-J.L.)
| | - Cheng-Hsun Lu
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, # 7 Chung-Shan South Road, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-F.C.); (K.-J.L.)
- Institute of Clinical Medicine, National Taiwan University College of Medicine, # 7 Chung-Shan South Road, Taipei 10002, Taiwan
| | - Chiao-Feng Cheng
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, # 7 Chung-Shan South Road, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-F.C.); (K.-J.L.)
- Institute of Clinical Medicine, National Taiwan University College of Medicine, # 7 Chung-Shan South Road, Taipei 10002, Taiwan
| | - Ko-Jen Li
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, # 7 Chung-Shan South Road, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-F.C.); (K.-J.L.)
| | - Yu-Min Kuo
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, # 7 Chung-Shan South Road, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-F.C.); (K.-J.L.)
| | - Cheng-Han Wu
- Department of Internal Medicine, National Taiwan University Hospital-Hsinchu Branch, # 2, Section 1, Shengyi Road, Hsinchu County 302058, Taiwan;
| | - Chin-Hsiu Liu
- Department of Internal Medicine, National Taiwan University Hospital-Yunlin Branch, # 579, Section 2, Yunlin Road, Yunlin County 640203, Taiwan;
| | - Song-Chou Hsieh
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, # 7 Chung-Shan South Road, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-F.C.); (K.-J.L.)
| | - Chang-Youh Tsai
- Department of Internal Medicine, Fu-Jen Catholic University Hospital, College of Medicine, Fu-Jen Catholic University, # 69 Guizi Road, New Taipei City 24352, Taiwan
| | - Chia-Li Yu
- Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, # 7 Chung-Shan South Road, Taipei 10002, Taiwan; (C.-Y.S.); (C.-H.L.); (C.-F.C.); (K.-J.L.)
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Rohilla M, Rishabh, Bansal S, Garg A, Dhiman S, Dhankhar S, Saini M, Chauhan S, Alsubaie N, Batiha GES, Albezrah NKA, Singh TG. Discussing pathologic mechanisms of Diabetic retinopathy & therapeutic potentials of curcumin and β-glucogallin in the management of Diabetic retinopathy. Biomed Pharmacother 2023; 169:115881. [PMID: 37989030 DOI: 10.1016/j.biopha.2023.115881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 11/04/2023] [Accepted: 11/09/2023] [Indexed: 11/23/2023] Open
Abstract
Diabetic retinopathy (DR) is a form of retinal microangiopathy that occurs as a result of long-term Diabetes mellitus (DM). Patients with Diabetes mellitus typically suffer from DR as a progression of the disease that may be due to initiation and dysregulation of pathways like the polyol, hexosamine, the AGE/RAGE, and the PKC pathway, which all have negative impacts on eye health and vision. In this review, various databases, including PubMed, Google Scholar, Web of Science, and Science Direct, were scoured for data relevant to the aforementioned title. The three most common therapies for DR today are retinal photocoagulation, anti-vascular endothelial growth factor (VEGF) therapy, and vitrectomy, however, there are a number of drawbacks and limits to these methods. So, it is of critical importance and profound interest to discover treatments that may successfully address the pathogenesis of DR. Curcumin and β-glucogallin are the two potent compounds of natural origin that are already being used in various nutraceutical formulations for several ailments. They have been shown potent antiapoptotic, anti-inflammatory, antioxidant, anticancer, and pro-vascular function benefits in animal experiments. Their parent plant species have been used for generations by practitioners of traditional herbal medicine for the treatment and prevention of various eye ailments. In this review, we will discuss about pathophysiology of Diabetic retinopathy and the therapeutic potentials of curcumin and β-glucogallin one of the principal compounds from Curcuma longa and Emblica officinalis in Diabetic retinopathy.
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Affiliation(s)
- Manni Rohilla
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India; Swami Vivekanand College of Pharmacy, Ram Nagar, Banur, Punjab 140601, India
| | - Rishabh
- M. M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana 133207, India
| | - Seema Bansal
- M. M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana 133207, India
| | - Anjali Garg
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India; Swami Devi Dyal College of Pharmacy, Golpura Barwala, Panchkula, Haryana 134118, India
| | - Sachin Dhiman
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India
| | - Sanchit Dhankhar
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India
| | - Monika Saini
- Swami Vivekanand College of Pharmacy, Ram Nagar, Banur, Punjab 140601, India; M. M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana 133207, India
| | - Samrat Chauhan
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India.
| | - Nawal Alsubaie
- Department of Pharmacy Practice, College of Pharmacy, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh, Saudi Arabia
| | - Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, AlBeheira, Egypt
| | - Nisreen Khalid Aref Albezrah
- Obstetric and Gynecology Department, Medicine College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
| | - Thakur Gurjeet Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab 140401, India.
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6
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Senavirathna L, Pan S, Chen R. Protein Advanced Glycation End Products and Their Implications in Pancreatic Cancer. Cancer Prev Res (Phila) 2023; 16:601-610. [PMID: 37578815 PMCID: PMC10843555 DOI: 10.1158/1940-6207.capr-23-0162] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 07/14/2023] [Accepted: 08/10/2023] [Indexed: 08/15/2023]
Abstract
Protein advanced glycation end products (AGE) formed by nonenzymatic glycation can disrupt the normal structure and function of proteins, and stimulate the receptor for AGEs (RAGE), triggering intricate mechanisms that are etiologically related to various chronic diseases, including pancreatic cancer. Many common risk factors of pancreatic cancer are the major sources for the formation of protein AGEs and glycative stress in the human body. Abnormal accumulation of protein AGEs can impair the cellular proteome and promote AGE-RAGE driven pro-inflammatory signaling cascades, leading to increased oxidative stress, protease resistance, protein dysregulation, transcription activity of STAT, NF-κB, and AP-1, aberrant status in ubiquitin-proteasome system and autophagy, as well as other molecular events that are susceptible for the carcinogenic transformation towards the development of neoplasms. Here, we review studies to highlight our understanding in the orchestrated molecular events in bridging the impaired proteome, dysregulated functional networks, and cancer hallmarks initiated upon protein AGE formation and accumulation in pancreatic cancer.
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Affiliation(s)
- Lakmini Senavirathna
- The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Sheng Pan
- The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
| | - Ru Chen
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
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7
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Mamilla M, Yartha SGR, Tuli R, Konipineni S, Rayaprolu DT, Borgharkar G, Kalluru PKR, Thugu TR. Role of Magnesium in Diabetic Nephropathy for Better Outcomes. Cureus 2023; 15:e43076. [PMID: 37692668 PMCID: PMC10484355 DOI: 10.7759/cureus.43076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/07/2023] [Indexed: 09/12/2023] Open
Abstract
Diabetic nephropathy (DN) is a major cause of end-stage renal disease worldwide, resulting from uncontrolled diabetes. Oxidative stress plays a critical role in the pathophysiology of DN, leading to cellular damage and disease progression. Magnesium, an essential mineral, has emerged as a potential therapeutic agent due to its antioxidative, anti-inflammatory, and antifibrotic properties. An extensive literature search was conducted on Medline using the keywords "Diabetic nephropathy," "Magnesium," and "Chronic Kidney Disease," and the results published after 2000 were exclusively studied to build this review. This review aims to summarize the role of magnesium in DN and explore its therapeutic potential. Magnesium acts as a cofactor for antioxidant enzymes, directly scavenges reactive oxygen species, and enhances the expression of antioxidant proteins. Furthermore, magnesium exhibits anti-inflammatory effects by suppressing pro-inflammatory cytokine production and inhibiting inflammatory signaling pathways. Magnesium supplementation has been shown to reduce oxidative stress markers and improve antioxidant enzyme activities in clinical studies. Additionally, magnesium has been found to mitigate renal fibrosis, maintain tubular integrity and function, improve endothelial function, and modulate renal hemodynamics. Although limited clinical trials suggest the renoprotective effects of magnesium in DN, further research is needed to determine the optimal dosage, duration, and long-term effects of magnesium supplementation. Despite existing drawbacks and gaps in the literature, magnesium holds promise as adjunctive therapy for DN by targeting oxidative stress and preserving renal function.
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Affiliation(s)
- Mahesh Mamilla
- Internal Medicine, Sri Venkateswara Medical College, Tirupati, IND
| | | | - Richa Tuli
- Internal Medicine, School of Medicine, Xiamen University, Xiamen, CHN
| | - Sunil Konipineni
- Internal Medicine, Zaporizhzhia State Medical University, Zaporizhzhia, UKR
| | | | - Gargi Borgharkar
- Public Health, University of Alabama at Birmingham, Birmingham, USA
| | | | - Thanmai Reddy Thugu
- Internal Medicine, Sri Padmavathi Medical College for Women, Sri Venkateswara Institute of Medical Sciences, Tirupati, IND
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Abstract
Diabetes mellitus is the ninth leading cause of mortality worldwide. It is a complex disease that manifests as chronic hyperglycemia. Glucose exposure causes biochemical changes at the proteome level as reflected in accumulation of glycated proteins. A prominent example is hemoglobin A1c (HbA1c), a glycated protein widely accepted as a diabetic indicator. Another emerging biomarker is glycated albumin which has demonstrated utility in situations where HbA1c cannot be used. Other proteins undergo glycation as well thus impacting cellular function, transport and immune response. Accordingly, these glycated counterparts may serve as predictors for diabetic complications and thus warrant further inquiry. Fortunately, modern proteomics has provided unique analytic capability to enable improved and more comprehensive exploration of glycating agents and glycated proteins. This review broadly covers topics from epidemiology of diabetes to modern analytical tools such as mass spectrometry to facilitate a better understanding of diabetes pathophysiology. This serves as an attempt to connect clinically relevant questions with findings of recent proteomic studies to suggest future avenues of diabetes research.
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Affiliation(s)
- Aleks Shin
- Department of Pathology & Anatomical Sciences, School of Medicine, University of Missouri, Columbia, MO, United States
| | - Shawn Connolly
- Department of Pathology & Anatomical Sciences, School of Medicine, University of Missouri, Columbia, MO, United States
| | - Kuanysh Kabytaev
- Department of Pathology & Anatomical Sciences, School of Medicine, University of Missouri, Columbia, MO, United States.
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9
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Hadzi-Petrushev N, Angelovski M, Mladenov M. Advanced Glycation End Products and Diabetes. CONTEMPORARY ENDOCRINOLOGY 2023:99-127. [DOI: 10.1007/978-3-031-39721-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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10
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Determination of hemoglobin-derived advanced glycation end products deploying metal salts in solution: Towards development of low-cost detection technique. J Mol Liq 2022. [DOI: 10.1016/j.molliq.2022.120338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Xu X, Ma C, Wu H, Ma Y, Liu Z, Zhong P, Jin C, Ning W, Wu X, Zhang Y, Han J, Wang J. Fructose Induces Pulmonary Fibrotic Phenotype Through Promoting Epithelial-Mesenchymal Transition Mediated by ROS-Activated Latent TGF-β1. Front Nutr 2022; 9:850689. [PMID: 35711535 PMCID: PMC9197188 DOI: 10.3389/fnut.2022.850689] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 04/21/2022] [Indexed: 12/12/2022] Open
Abstract
Fructose is a commonly used food additive and has many adverse effects on human health, but it is unclear whether fructose impacts pulmonary fibrosis. TGF-β1, a potent fibrotic inducer, is produced as latent complexes by various cells, including alveolar epithelial cells, macrophages, and fibroblasts, and must be activated by many factors such as reactive oxygen species (ROS). This study explored the impact of fructose on pulmonary fibrotic phenotype and epithelial-mesenchymal transition (EMT) using lung epithelial cells (A549 or BEAS-2B) and the underlying mechanisms. Fructose promoted the cell viability of lung epithelial cells, while N-Acetyl-l-cysteine (NAC) inhibited such. Co-treatment of fructose and latent TGF-β1 could induce the fibrosis phenotype and the epithelial-mesenchymal transition (EMT)-related protein expression, increasing lung epithelial cell migration and invasion. Mechanism analysis shows that fructose dose-dependently promoted the production of total and mitochondrial ROS in A549 cells, while NAC eliminated this promotion. Notably, post-administration with NAC or SB431542 (a potent TGF-β type I receptor inhibitor) inhibited fibrosis phenotype and EMT process of lung epithelial cells co-treated with fructose and latent TGF-β1. Finally, the fibrosis phenotype and EMT-related protein expression of lung epithelial cells were mediated by the ROS-activated latent TGF-β1/Smad3 signal. This study revealed that high fructose promoted the fibrotic phenotype of human lung epithelial cells by up-regulating oxidative stress, which enabled the latent form of TGF-β1 into activated TGF-β1, which provides help and reference for the diet adjustment of healthy people and patients with fibrosis.
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Affiliation(s)
- Xiaoxiao Xu
- Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
| | - Chuang Ma
- Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
| | - Hang Wu
- Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
| | - Yuanqiao Ma
- Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
| | - Zejin Liu
- Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
| | - Peijie Zhong
- Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
| | - Chaolei Jin
- Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
| | - Wenjuan Ning
- Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
| | - Xiao Wu
- Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
| | - Yijie Zhang
- Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
| | - Jichang Han
- Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
| | - Junpeng Wang
- Infection and Immunity Institute and Translational Medical Center of Huaihe Hospital, Henan University, Kaifeng, China
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12
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Choi LS, Ahmed K, Kim YS, Yim JE. Skin accumulation of advanced glycation end products and cardiovascular risk in Korean patients with type 2 diabetes mellitus. Heliyon 2022; 8:e09571. [PMID: 35711980 PMCID: PMC9192809 DOI: 10.1016/j.heliyon.2022.e09571] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/01/2022] [Accepted: 05/25/2022] [Indexed: 12/02/2022] Open
Abstract
Background The formation of advanced glycation end products (AGEs) takes place during normal aging; however, their production is faster in people having diabetes. The accumulated AGEs reportedly play a role in the occurrence of various age-related disorders. Furthermore, the skin autofluorescence (SAF) technique can be used to detect accumulated AGEs levels. There are few reports on the association between skin accumulation of AGEs and risk of complications in type 2 diabetes mellitus. Methods In this study, we aimed to describe the association between the skin accumulation of AGEs and cardiovascular risk factors in Korean patients with type 2 diabetes. A total of 310 Korean patients with diabetes were enrolled, and the levels of AGEs were measured using SAP. Levels of fasting blood glucose (FBS), triglycerides, total cholesterol, low- and high-density lipoprotein cholesterol, proteinuria, arterial pulse wave velocity (PWV), and blood vessel age were measured using an automatic waveform analyzer. General linear models were used to identify the independent effect of AGEs after adjusting for covariates (age, weight, and duration of diabetes). Results The skin levels of AGEs were strongly correlated with the diabetes duration. Significant independent associations were observed for AGEs with FBS (P < 0.01), proteinuria (P < 0.001), and PWV (P < 0.001). The advanced glycated product was independently associated to the arterial pulse wave conduction velocity that is used as a representative method for measuring arteriosclerosis by analysis early cardiovascular risk factors. Conclusion Our results show that an increase in SAF levels in Korean patients with type 2 diabetes is associated with PWV and vein age, and thereby with arterial stiffness. Therefore, our results suggest that AGEs are associated with cardiovascular risk factors. The level of AGEs can thus be used as an indicator of cardiovascular diseases in the clinical diagnosis of patients with type 2 diabetes.
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Affiliation(s)
- Lee-Seoul Choi
- Department of Food and Nutrition, Changwon National University, Changwon, South Korea
| | - Kainat Ahmed
- Interdisciplinary Program in Senior Human Ecology, Changwon National University, Changwon, South Korea
| | - Young-Seol Kim
- Department of Endocrinology, Kyung Hee Medical Center, Seoul, South Korea
| | - Jung-Eun Yim
- Department of Food and Nutrition, Changwon National University, Changwon, South Korea
- Interdisciplinary Program in Senior Human Ecology, Changwon National University, Changwon, South Korea
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13
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Schmutzler S, Wölk M, Hoffmann R. Differentiation and Quantitation of Coeluting Isomeric Amadori and Heyns Peptides Using Sugar-Specific Fragment Ion Ratios. Anal Chem 2022; 94:7909-7917. [PMID: 35609340 DOI: 10.1021/acs.analchem.2c00681] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
d-glucose and d-fructose present in blood, tissues, and organs of all mammals can react with amino groups, leading to glucated (Amadori) and fructated (Heyns) products, i.e., proteins glycated at lysine residues. While typically present at low concentration in humans, metabolic diseases including diabetes elevate sugar levels, favoring glycation and consecutive reactions leading to advanced glycation end products (AGEs) linked to diabetic complications and cardiovascular diseases. Analytical methods able to differentiate and to individually quantify Amadori- and Heyns-modified proteins in complex sample mixtures, e.g., serum, are still very limited. Here, we show that the reported and supposedly specific neutral losses displayed in tandem mass spectra of Heyns peptides cannot be used for a reliable differentiation as they were also observed for Amadori peptides. However, the combination of several neutral loss signals in fragment ion ratios at both precursor and fragment ion signals allowed the differentiation and relative quantitation of coeluting isomeric Amadori and Heyns peptides at different concentrations and peptide ratios. This was also true for digested human plasma. Thus, the presented strategy allows the quantitation of Amadori and Heyns peptides in complex samples, especially by spiking isotope-labeled peptides. This will allow searching for glucated and fructated biomarkers in clinical samples.
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Affiliation(s)
- Sebastian Schmutzler
- Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, 04103 Leipzig, Germany.,Center for Biotechnology and Biomedicine, Universität Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany
| | - Michele Wölk
- Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, 04103 Leipzig, Germany.,Center for Biotechnology and Biomedicine, Universität Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany
| | - Ralf Hoffmann
- Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Universität Leipzig, 04103 Leipzig, Germany.,Center for Biotechnology and Biomedicine, Universität Leipzig, Deutscher Platz 5, 04103 Leipzig, Germany
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14
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León-García MC, Silva-Gaona OG, Hernández-Ortiz M, Vargas-Ortiz K, Ramírez-Emiliano J, Garay-Sevilla ME, Encarnación-Guevara S, Pérez-Vázquez V. Curcumin Prevents the Glycation of Tricarboxylic Acid Cycle and Cell Respiration Proteins in the Heart of Mice Fed with a High-Fructose Diet. Curr Pharm Des 2022; 28:1769-1778. [PMID: 35362381 DOI: 10.2174/1381612828666220331160501] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 02/24/2022] [Indexed: 11/22/2022]
Abstract
BACKGROUND A high fructose diet (HFD) induces protein glycation. The latter is related to a higher risk of cardiovascular disease. Curcumin is a natural pleiotropic compound that may possess antiglycant properties. OBJECTIVE To analyze the effect of curcumin on the content of glycated proteins in the hearts of 6-week-old mice fed with a HFD for 15 weeks. METHODS Mice were allocated in four groups (n = 6/group): a control group that received a standard diet (CT); a group that received 30% w/v fructose in water (F); a group that received 0.75% w/w curcumin supplemented in food (C); a group that received 30% w/v fructose in water and 0.75% w/w curcumin supplemented in food (F+C). The content of glycated proteins in the heart was determined by Western Blot (whereas the spots were detected by 2D-PAGE) using anti-AGE and anti-CML antibodies. A densitometric analysis was performed using the ImageLab software. Glycated proteins were identified by MALDI-TOF-MS, and an ontological analysis was performed in terms of biological processes and molecular function based on the STRING and DAVID databases. RESULTS Fourteen glycated protein spots were detected, two of them with anti-AGE and the other 12 with anti-CML. In total, eleven glycated proteins were identified, out of which three had decreased glycation levels due to curcumin exposure. The identified proteins participate in processes such as cellular respiration, oxidative phosphorylation, lipid metabolism, carbohydrate metabolism, the tricarboxylic acid cycle (TAC), and the organization of intermediate filaments. CONCLUSIONS Curcumin decreased the fructose-induced glycation level of the ACO2, NDUFS7, and DLAT proteins.
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Affiliation(s)
- María Cristina León-García
- Dpto. de Ciencias Médicas, División de Ciencias de la Salud, Campus León, Universidad de Guanajuato, León, Guanajuato, México
| | - Oscar Gerardo Silva-Gaona
- Dpto. de Ciencias Médicas, División de Ciencias de la Salud, Campus León, Universidad de Guanajuato, León, Guanajuato, México
| | | | - Katya Vargas-Ortiz
- Dpto. de Ciencias Médicas, División de Ciencias de la Salud, Campus León, Universidad de Guanajuato, León, Guanajuato, México
| | - Joel Ramírez-Emiliano
- Dpto. de Ciencias Médicas, División de Ciencias de la Salud, Campus León, Universidad de Guanajuato, León, Guanajuato, México
| | - Ma Eugenia Garay-Sevilla
- Dpto. de Ciencias Médicas, División de Ciencias de la Salud, Campus León, Universidad de Guanajuato, León, Guanajuato, México
| | | | - Victoriano Pérez-Vázquez
- Dpto. de Ciencias Médicas, División de Ciencias de la Salud, Campus León, Universidad de Guanajuato, León, Guanajuato, México
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15
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The Association between Accumulation of Toxic Advanced Glycation End-Products and Cytotoxic Effect in MC3T3-E1 Cells. Nutrients 2022; 14:nu14050990. [PMID: 35267965 PMCID: PMC8912344 DOI: 10.3390/nu14050990] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 02/22/2022] [Accepted: 02/24/2022] [Indexed: 02/01/2023] Open
Abstract
In diabetic patients, the metabolism of excess glucose increases the toxicity of the aldehyde group of sugar. Aldehydes, including glyceraldehyde (GA), react with intracellular proteins to form advanced glycation end-products (AGEs), which deteriorate bone quality and cause osteoporosis. One of the causes of osteoporotic fractures is impaired osteoblast osteogenesis; however, the cytotoxic effects of aldehydes and the subsequent formation of AGEs in osteoblasts have not yet been examined in detail. Therefore, the present study investigated the cytotoxicity of intracellular GA and GA-derived AGEs, named toxic AGEs (TAGE), in the mouse osteoblastic cell line MC3T3-E1. Treatment with GA induced MC3T3-E1 cell death, which was accompanied by TAGE modifications in several intracellular proteins. Furthermore, the downregulated expression of Runx2, a transcription factor essential for osteoblast differentiation, and collagen correlated with the accumulation of TAGE. The GA treatment also reduced the normal protein levels of collagen in cells, suggesting that collagen may be modified by TAGE and form an abnormal structure. Collectively, the present results show for the first time that GA and TAGE exert cytotoxic effects in osteoblasts, inhibit osteoblastic differentiation, and decrease the amount of normal collagen. The suppression of GA production and associated accumulation of TAGE has potential as a novel therapeutic target for osteoporosis under hyperglycemic conditions.
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16
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Muraoka MY, Justino AB, Caixeta DC, Queiroz JS, Sabino-Silva R, Salmen Espindola F. Fructose and methylglyoxal-induced glycation alters structural and functional properties of salivary proteins, albumin and lysozyme. PLoS One 2022; 17:e0262369. [PMID: 35061788 PMCID: PMC8782344 DOI: 10.1371/journal.pone.0262369] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 12/21/2021] [Indexed: 01/08/2023] Open
Abstract
Glycation process refers to reactions between reduction sugars and amino acids that can lead to formation of advanced glycation end products (AGEs) which are related to changes in chemical and functional properties of biological structures that accumulate during aging and diseases. The aim of this study was to perform and analyze in vitro glycation by fructose and methylglyoxal (MGO) using salivary fluid, albumin, lysozyme, and salivary α-amylase (sAA). Glycation effect was analyzed by biochemical and spectroscopic methods. The results were obtained by fluorescence analysis, infrared spectroscopy (total attenuated reflection-Fourier transform, ATR-FTIR) followed by multivariate analysis of principal components (PCA), protein profile, immunodetection, enzymatic activity and oxidative damage to proteins. Fluorescence increased in all glycated samples, except in saliva with fructose. The ATR-FTIR spectra and PCA analysis showed structural changes related to the vibrational mode of glycation of albumin, lysozyme, and salivary proteins. Glycation increased the relative molecular mass (Mr) in protein profile of albumin and lysozyme. Saliva showed a decrease in band intensity when glycated. The analysis of sAA immunoblotting indicated a relative reduction in intensity of its correspondent Mr after sAA glycation; and a decrease in its enzymatic activity was observed. Carbonylation levels increased in all glycated samples, except for saliva with fructose. Thiol content decreased only for glycated lysozyme and saliva with MGO. Therefore, glycation of salivary fluid and sAA may have the potential to identify products derived by glycation process. This opens perspectives for further studies on the use of saliva, an easy and non-invasive collection fluid, to monitor glycated proteins in the aging process and evolution of diseases.
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Affiliation(s)
- Mariane Yumiko Muraoka
- Biochemistry and Molecular Biology Laboratory, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil
| | - Allisson Benatti Justino
- Biochemistry and Molecular Biology Laboratory, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil
| | - Douglas Carvalho Caixeta
- Biochemistry and Molecular Biology Laboratory, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil
- Innovation Center in Salivary Diagnostic and Nanotheranostics, Institute of Biomedical Sciences, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil
| | - Julia Silveira Queiroz
- Biochemistry and Molecular Biology Laboratory, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil
| | - Robinson Sabino-Silva
- Innovation Center in Salivary Diagnostic and Nanotheranostics, Institute of Biomedical Sciences, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil
| | - Foued Salmen Espindola
- Biochemistry and Molecular Biology Laboratory, Institute of Biotechnology, Federal University of Uberlandia, Uberlandia, Minas Gerais, Brazil
- * E-mail:
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17
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Martin-Morales A, Arakawa T, Sato M, Matsumura Y, Mano-Usui F, Ikeda K, Inagaki N, Sato K. Development of a Method for Quantitation of Glyceraldehyde in Various Body Compartments of Rodents and Humans. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2021; 69:13246-13254. [PMID: 34702032 DOI: 10.1021/acs.jafc.1c03177] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
There is limited information available about the physiological content of glyceraldehyde, a precursor of toxic advanced glycation end products. The conventional derivatization method for aldoses using 1-phenyl-3-methyl-5-pyrazolone did not allow reproducible quantification of glyceraldehyde due to the instability of glyceraldehyde compared to other aldoses. We optimized the derivatization condition to achieve high and reproducible recovery of derivatives for liquid chromatography tandem mass spectrometry quantification. Based on the stability of glyceraldehyde during sample preparation and high recovery of spiked standard, the present method provides reproducible quantification of glyceraldehyde in the body. The glyceraldehyde contents in fasting conditions in the rodent liver (mice: 50.0 ± 3.9 nmol/g; rats: 35.5 ± 4.9 nmol/g) were higher than those in plasma (9.4 ± 1.7 and 7.2 ± 1.2 nmol/mL). The liver glyceraldehyde levels significantly increased after food consumption (p < 0.05) but remained constant in the plasma. High fat diet feeding significantly increased plasma glyceraldehyde levels in mice (p < 0.005). In healthy human volunteers, the plasma glyceraldehyde levels remained unchanged after the consumption of steamed rice. In patients with type 2 diabetes, the plasma glyceraldehyde level was positively correlated with the plasma glucose level (r = 0.84; p < 0.0001).
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Affiliation(s)
- Agustin Martin-Morales
- Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Kyoto 606 8054, Japan
| | - Takanori Arakawa
- Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Kyoto 606 8054, Japan
| | - Mona Sato
- Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Kyoto 606 8054, Japan
| | - Yasuki Matsumura
- Division of Agronomy and Horticultural Science, Graduate School of Agriculture, Kyoto University, Gokasho, Uji, Kyoto 611 0011, Japan
| | - Fumika Mano-Usui
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Kyoto 606 8507, Japan
| | - Kaori Ikeda
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Kyoto 606 8507, Japan
| | - Nobuya Inagaki
- Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Kyoto 606 8507, Japan
| | - Kenji Sato
- Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Kyoto 606 8054, Japan
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18
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Liu JJ, You Y, Gao SQ, Tang S, Chen L, Wen GB, Lin YW. Identification of the Protein Glycation Sites in Human Myoglobin as Rapidly Induced by d-Ribose. Molecules 2021; 26:molecules26195829. [PMID: 34641382 PMCID: PMC8512392 DOI: 10.3390/molecules26195829] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 09/22/2021] [Accepted: 09/23/2021] [Indexed: 12/11/2022] Open
Abstract
Protein glycation is an important protein post-translational modification and is one of the main pathogenesis of diabetic angiopathy. Other than glycated hemoglobin, the protein glycation of other globins such as myoglobin (Mb) is less studied. The protein glycation of human Mb with ribose has not been reported, and the glycation sites in the Mb remain unknown. This article reports that d-ribose undergoes rapid protein glycation of human myoglobin (HMb) at lysine residues (K34, K87, K56, and K147) on the protein surface, as identified by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). Moreover, glycation by d-ribose at these sites slightly decreased the rate of the met heme (FeIII) in reaction with H2O2 to form a ferryl heme (FeIV=O). This study provides valuable insight into the protein glycation by d-ribose and provides a foundation for studying the structure and function of glycated heme proteins.
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Affiliation(s)
- Jing-Jing Liu
- School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China; (J.-J.L.); (S.T.); (L.C.)
| | - Yong You
- Laboratory of Protein Structure and Function, University of South China, Hengyang 421001, China; (Y.Y.); (S.-Q.G.); (G.-B.W.)
| | - Shu-Qin Gao
- Laboratory of Protein Structure and Function, University of South China, Hengyang 421001, China; (Y.Y.); (S.-Q.G.); (G.-B.W.)
| | - Shuai Tang
- School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China; (J.-J.L.); (S.T.); (L.C.)
| | - Lei Chen
- School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China; (J.-J.L.); (S.T.); (L.C.)
| | - Ge-Bo Wen
- Laboratory of Protein Structure and Function, University of South China, Hengyang 421001, China; (Y.Y.); (S.-Q.G.); (G.-B.W.)
| | - Ying-Wu Lin
- School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, China; (J.-J.L.); (S.T.); (L.C.)
- Laboratory of Protein Structure and Function, University of South China, Hengyang 421001, China; (Y.Y.); (S.-Q.G.); (G.-B.W.)
- Correspondence: ; Tel.: +86-734-8282375
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19
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Jiang H, Lin Q, Ma L, Luo S, Jiang X, Fang J, Lu Z. Fructose and fructose kinase in cancer and other pathologies. J Genet Genomics 2021; 48:531-539. [PMID: 34326012 DOI: 10.1016/j.jgg.2021.06.006] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 06/22/2021] [Accepted: 06/22/2021] [Indexed: 12/14/2022]
Abstract
Fructose metabolism and fructose kinase KHK-C/A are key factors in the development of lipid oversynthesis-promoted metabolic disorders and cancer. Here, we summarize and discuss the current knowledge about the specific features of fructose metabolism and the distinct roles of KHK-C and KHK-A in metabolic liver diseases and their relevant metabolic disorders and cancer, and we highlight the specific protein kinase activity of KHK-A in tumor development. In addition, different approaches that have been used to inhibit KHK and the exploration of KHK inhibitors in clinical treatment are introduced.
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Affiliation(s)
- Hongfei Jiang
- Cancer Institute of The Affiliated Hospital of Qingdao University and Qingdao Cancer Institute, Qingdao 266061, China
| | - Qian Lin
- Cancer Institute of The Affiliated Hospital of Qingdao University and Qingdao Cancer Institute, Qingdao 266061, China
| | - Leina Ma
- Cancer Institute of The Affiliated Hospital of Qingdao University and Qingdao Cancer Institute, Qingdao 266061, China
| | - Shudi Luo
- Zhejiang University Cancer Center, Hangzhou 310029, China
| | - Xiaoming Jiang
- Zhejiang University Cancer Center, Hangzhou 310029, China
| | - Jing Fang
- Cancer Institute of The Affiliated Hospital of Qingdao University and Qingdao Cancer Institute, Qingdao 266061, China.
| | - Zhimin Lu
- Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310029, China; Zhejiang University Cancer Center, Hangzhou 310029, China.
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20
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Annandale M, Daniels LJ, Li X, Neale JPH, Chau AHL, Ambalawanar HA, James SL, Koutsifeli P, Delbridge LMD, Mellor KM. Fructose Metabolism and Cardiac Metabolic Stress. Front Pharmacol 2021; 12:695486. [PMID: 34267663 PMCID: PMC8277231 DOI: 10.3389/fphar.2021.695486] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 06/07/2021] [Indexed: 11/13/2022] Open
Abstract
Cardiovascular disease is one of the leading causes of mortality in diabetes. High fructose consumption has been linked with the development of diabetes and cardiovascular disease. Serum and cardiac tissue fructose levels are elevated in diabetic patients, and cardiac production of fructose via the intracellular polyol pathway is upregulated. The question of whether direct myocardial fructose exposure and upregulated fructose metabolism have potential to induce cardiac fructose toxicity in metabolic stress settings arises. Unlike tightly-regulated glucose metabolism, fructose bypasses the rate-limiting glycolytic enzyme, phosphofructokinase, and proceeds through glycolysis in an unregulated manner. In vivo rodent studies have shown that high dietary fructose induces cardiac metabolic stress and functional disturbance. In vitro, studies have demonstrated that cardiomyocytes cultured in high fructose exhibit lipid accumulation, inflammation, hypertrophy and low viability. Intracellular fructose mediates post-translational modification of proteins, and this activity provides an important mechanistic pathway for fructose-related cardiomyocyte signaling and functional effect. Additionally, fructose has been shown to provide a fuel source for the stressed myocardium. Elucidating the mechanisms of fructose toxicity in the heart may have important implications for understanding cardiac pathology in metabolic stress settings.
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Affiliation(s)
- M Annandale
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - L J Daniels
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.,Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - X Li
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - J P H Neale
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - A H L Chau
- Department of Physiology, School of Biomedical Sciences, University of Melbourne, Melbourne, VIC, Australia
| | - H A Ambalawanar
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - S L James
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - P Koutsifeli
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
| | - L M D Delbridge
- Department of Physiology, School of Biomedical Sciences, University of Melbourne, Melbourne, VIC, Australia
| | - K M Mellor
- Department of Physiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.,Department of Physiology, School of Biomedical Sciences, University of Melbourne, Melbourne, VIC, Australia
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21
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Vafadar Ghasemi L, Behnam Rassouli M, Matin MM, Mahdavi-Shahri N. Benfotiamine reduced collagen IV contents of sciatic nerve in hyperglycemic rats. J Diabetes Metab Disord 2021; 20:21-30. [PMID: 34222057 PMCID: PMC8212243 DOI: 10.1007/s40200-020-00666-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Accepted: 10/19/2020] [Indexed: 01/13/2023]
Abstract
BACKGROUND Neuropathy as a common complication of hyperglycemia in diabetic patients is probably caused by metabolic and structural changes in extracellular matrix (ECM) of peripheral nerves. This study was designed to evaluate the effects of benfotiamine (BT) on the structural, biological and mechanical characteristics of rat sciatic nerve in hyperglycemic condition. MATERIALS AND METHODS Forty eight adult male Wistar rats were assigned to 6 groups (n = 8): control (healthy rats with no treatment; C), positive control (healthy rats received BT treatment; B), negative control groups 1&2 (hyperglycemic rats kept for 4 and/or 8 weeks; 4WD and 8WD, respectively) and experimental groups 1&2 (hyperglycemic rats treated by daily oral gavage of 100 mg kg- 1 body weight BT for 4 and/or 8 weeks; 4WD + BT and 8WD + BT, respectively). Hyperglycemia was induced by a single intraperitoneal injection of of streptozotocin (55 mg kg- 1 body weight). After a period of experimental period (4 and/or 8 weeks) rats were sacrificed and from each two segments (1 cm length) of left sciatic nerve were sampled. These samples were prepared for histological examinations (light and electron microscopy), collagen IV immunohistochemistry and strength tensile test. RESULTS In comparison to control groups, in 4WD and 8WD groups the amount of type IV collagen was increased, the structure of myelin sheath and nerve fibers were extensively altered and the tensile strength was significantly decreased (p < 0.05) while in 4WD + BT and 8WD + BT groups these abnormalities were attenuated. CONCLUSIONS It seems that BT treatment may rescue the sciatic nerve from the hyperglycemic-induced ECM structural abnormality. This beneficial advantage of BT is likely exerted through the modification of glucose metabolism pathways.
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Affiliation(s)
- Leila Vafadar Ghasemi
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Azadi Square, Mashhad, Iran
- Department of Biology, Faculty of Sciences, University of Zabol, Zabol, Iran
| | - Morteza Behnam Rassouli
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Azadi Square, Mashhad, Iran
| | - Maryam M. Matin
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Azadi Square, Mashhad, Iran
- Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
| | - Naser Mahdavi-Shahri
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Azadi Square, Mashhad, Iran
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22
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Golonka RM, Cooper JK, Issa R, Devarasetty PP, Gokula V, Busken J, Zubcevic J, Hill J, Vijay-Kumar M, Menon B, Joe B. Impact of Nutritional Epigenetics in Essential Hypertension: Targeting microRNAs in the Gut-Liver Axis. Curr Hypertens Rep 2021; 23:28. [PMID: 33961141 PMCID: PMC8105193 DOI: 10.1007/s11906-021-01142-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/25/2021] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW To review the current knowledge on interactions between dietary factors and microRNAs (miRNAs) in essential hypertension (EH) pathogenesis. RECENT FINDINGS There exists an integration of maintenance signals generated by genetic, epigenetic, immune, and environmental (e.g., dietary) factors that work to sustain balance in the gut-liver axis. It is well established that an imbalance in this complex, intertwined system substantially increases the risk for EH. As such, pertinent research has been taken to decipher how each signal operates in isolation and together in EH progression. Recent literature indicates that both macro- and micronutrients interrupt regulatory miRNA expressions and thus, alter multiple cellular processes that contribute to EH and its comorbidities. We highlight how carbohydrates, lipids, proteins, salt, and potassium modify miRNA signatures during EH. The disruption in miRNA expression can negatively impact communication systems such as over activating the renin-angiotensin-aldosterone system, modulating the vascular smooth muscle cell phenotype, and promoting angiogenesis to favor EH. We also delineate the prognostic value of miRNAs in EH and discuss the pros and cons of surgical vs dietary prophylactic approaches in EH prevention. We propose that dietary-dependent perturbation of the miRNA profile is one mechanism within the gut-liver axis that dictates EH development.
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Affiliation(s)
- Rachel M Golonka
- Microbiome Consortium, Center for Hypertension and Precision Medicine, Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Block Health Science Bldg, 3000 Arlington Ave, Toledo, OH, 43614, USA
| | | | - Rochell Issa
- The University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
| | | | - Veda Gokula
- The University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
| | - Joshua Busken
- The University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
| | - Jasenka Zubcevic
- Microbiome Consortium, Center for Hypertension and Precision Medicine, Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Block Health Science Bldg, 3000 Arlington Ave, Toledo, OH, 43614, USA
- Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, College of Veterinary Medicine, University of Florida, Gainesville, FL, 32611, USA
| | - Jennifer Hill
- Microbiome Consortium, Center for Hypertension and Precision Medicine, Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Block Health Science Bldg, 3000 Arlington Ave, Toledo, OH, 43614, USA
| | - Matam Vijay-Kumar
- Microbiome Consortium, Center for Hypertension and Precision Medicine, Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Block Health Science Bldg, 3000 Arlington Ave, Toledo, OH, 43614, USA
| | - Bindu Menon
- Department of Medical Education, University of Toledo College of Medicine and Life Sciences, Room 3105B, CCE Bldg, 2920 Arlington Ave, Toledo, OH, 43614, USA.
| | - Bina Joe
- Microbiome Consortium, Center for Hypertension and Precision Medicine, Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Block Health Science Bldg, 3000 Arlington Ave, Toledo, OH, 43614, USA.
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Bravo-Ruiz I, Medina MÁ, Martínez-Poveda B. From Food to Genes: Transcriptional Regulation of Metabolism by Lipids and Carbohydrates. Nutrients 2021; 13:nu13051513. [PMID: 33946267 PMCID: PMC8145205 DOI: 10.3390/nu13051513] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Accepted: 04/28/2021] [Indexed: 12/31/2022] Open
Abstract
Lipids and carbohydrates regulate gene expression by means of molecules that sense these macronutrients and act as transcription factors. The peroxisome proliferator-activated receptor (PPAR), activated by some fatty acids or their derivatives, and the carbohydrate response element binding protein (ChREBP), activated by glucose-derived metabolites, play a key role in metabolic homeostasis, especially in glucose and lipid metabolism. Furthermore, the action of both factors in obesity, diabetes and fatty liver, as well as the pharmacological development in the treatment of these pathologies are indeed of high relevance. In this review we present an overview of the discovery, mechanism of activation and metabolic functions of these nutrient-dependent transcription factors in different tissues contexts, from the nutritional genomics perspective. The possibility of targeting these factors in pharmacological approaches is also discussed. Lipid and carbohydrate-dependent transcription factors are key players in the complex metabolic homeostasis, but these factors also drive an adaptive response to non-physiological situations, such as overeating. Possibly the decisive role of ChREBP and PPAR in metabolic regulation points to them as ideal therapeutic targets, but their pleiotropic functions in different tissues makes it difficult to "hit the mark".
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Affiliation(s)
- Inés Bravo-Ruiz
- Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, E-29071 Málaga, Spain; (I.B.-R.); (M.Á.M.)
| | - Miguel Ángel Medina
- Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, E-29071 Málaga, Spain; (I.B.-R.); (M.Á.M.)
- Instituto de Investigación Biomédica de Málaga (IBIMA), E-29071 Málaga, Spain
- CIBER de Enfermedades Raras (CIBERER), E-29071 Málaga, Spain
| | - Beatriz Martínez-Poveda
- Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, E-29071 Málaga, Spain; (I.B.-R.); (M.Á.M.)
- Instituto de Investigación Biomédica de Málaga (IBIMA), E-29071 Málaga, Spain
- CIBER de Enfermedades Cardiovasculares (CIBERCV), E-28029 Madrid, Spain
- Correspondence:
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Federico A, Rosato V, Masarone M, Torre P, Dallio M, Romeo M, Persico M. The Role of Fructose in Non-Alcoholic Steatohepatitis: Old Relationship and New Insights. Nutrients 2021; 13:1314. [PMID: 33923525 PMCID: PMC8074203 DOI: 10.3390/nu13041314] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 04/12/2021] [Accepted: 04/14/2021] [Indexed: 12/22/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents the result of hepatic fat overload not due to alcohol consumption and potentially evolving to advanced fibrosis, cirrhosis, and hepatocellular carcinoma. Fructose is a naturally occurring simple sugar widely used in food industry linked to glucose to form sucrose, largely contained in hypercaloric food and beverages. An increasing amount of evidence in scientific literature highlighted a detrimental effect of dietary fructose consumption on metabolic disorders such as insulin resistance, obesity, hepatic steatosis, and NAFLD-related fibrosis as well. An excessive fructose consumption has been associated with NAFLD development and progression to more clinically severe phenotypes by exerting various toxic effects, including increased fatty acid production, oxidative stress, and worsening insulin resistance. Furthermore, some studies in this context demonstrated even a crucial role in liver cancer progression. Despite this compelling evidence, the molecular mechanisms by which fructose elicits those effects on liver metabolism remain unclear. Emerging data suggest that dietary fructose may directly alter the expression of genes involved in lipid metabolism, including those that increase hepatic fat accumulation or reduce hepatic fat removal. This review aimed to summarize the current understanding of fructose metabolism on NAFLD pathogenesis and progression.
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Affiliation(s)
- Alessandro Federico
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (M.D.); (M.R.)
| | - Valerio Rosato
- Internal Medicine and Hepatology Division, Department of Medicine, Surgery and Odontostomatology, “Scuola Medica Salernitana”, University of Salerno, 84084 Salerno, Italy; (V.R.); (M.M.); (P.T.); (M.P.)
- Liver Unit, Ospedale Evangelico Betania, 80147 Naples, Italy
| | - Mario Masarone
- Internal Medicine and Hepatology Division, Department of Medicine, Surgery and Odontostomatology, “Scuola Medica Salernitana”, University of Salerno, 84084 Salerno, Italy; (V.R.); (M.M.); (P.T.); (M.P.)
| | - Pietro Torre
- Internal Medicine and Hepatology Division, Department of Medicine, Surgery and Odontostomatology, “Scuola Medica Salernitana”, University of Salerno, 84084 Salerno, Italy; (V.R.); (M.M.); (P.T.); (M.P.)
| | - Marcello Dallio
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (M.D.); (M.R.)
| | - Mario Romeo
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (M.D.); (M.R.)
| | - Marcello Persico
- Internal Medicine and Hepatology Division, Department of Medicine, Surgery and Odontostomatology, “Scuola Medica Salernitana”, University of Salerno, 84084 Salerno, Italy; (V.R.); (M.M.); (P.T.); (M.P.)
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25
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Glyceraldehyde-derived advanced glycation end-products having pyrrolopyridinium-based crosslinks. Biochem Biophys Rep 2021; 26:100963. [PMID: 33748437 PMCID: PMC7960790 DOI: 10.1016/j.bbrep.2021.100963] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 01/10/2021] [Accepted: 02/22/2021] [Indexed: 11/21/2022] Open
Abstract
Reducing sugars and reactive aldehydes, such as glyceraldehyde, non-enzymatically react with amino or guanidino groups of proteins to form advanced glycation end-products (AGEs) by the Maillard reaction that involves Schiff base formation followed by Amadori rearrangement. AGEs are found relatively in abundance in the human eye and to accumulate at a higher rate in diseases that impair vision such as cataract, diabetic retinopathy or age-related macular degeneration. We identified two novel AGEs of pyrrolopyridinium lysine dimer derived from glyceraldehyde, PPG1 and PPG2, in the Maillard reaction of N α-acetyl-l-lysine with glyceraldehyde under physiological conditions. Having fluorophores similar to that of vesperlysine A, which was isolated from the human lens, PPGs were found to act as photosensitizers producing singlet oxygen in response to blue light irradiation. Moreover, PPG2 interacts with receptor for AGE (RAGE) in vitro with a higher binding affinity than GLAP, a well-known ligand of the receptor. We also proposed a pathway to form PPGs and discussed how they would be formed in vitro. As glyceraldehyde-derived AGEs have been studied extensively in connection with various hyperglycemia-related diseases, further studies will be required to find PPGs in vivo such as in the lens or other tissues.
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26
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Shaikh M, Siddiqui S, Zafar H, Naqeeb U, Subzwari F, Imad R, Khan KM, Choudhary MI. Antiglycation Activity of Triazole Schiff's Bases Against Fructosemediated Glycation: In Vitro and In Silico Study. Med Chem 2021; 16:575-591. [PMID: 30747076 DOI: 10.2174/1573406415666190212105718] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Revised: 01/22/2019] [Accepted: 02/04/2019] [Indexed: 02/01/2023]
Abstract
BACKGROUND Advanced glycation end products (AGEs) are known to be involved in the pathophysiology of diabetic complications, neurodegenerative diseases, and aging. Preventing the formation of AGEs can be helpful in the management of these diseases. OBJECTIVES Two classes of previously synthesized traizole Schiff's bases (4H-1,2,4-triazole-4- Schiff's bases 1-14, and 4H-1,2,4-triazole-3-Schiff's bases 15-23) were evaluated for their in vitro antiglycation activity. METHODS In vitro fructose-mediated human serum albumin (HSA) glycation assay was employed to assess the antiglycation activity of triazole Schiff's bases. The active compounds were subjected to cytotoxicity analysis by MTT assay on mouse fibroblast (3T3) cell line. Molecular docking and simulation studies were carried out to evaluate the interactions and stability of compounds with HSA. Anti-hyperglycemic and antioxidant activities of selected non-cytotoxic compounds were evaluated by in vitro α-glucosidase inhibition, and DPPH free radical scavenging assays, respectively. RESULTS Compound 1 (IC50=47.30±0.38 µM) from 4H-1,2,4-triazole-4-Schiff's bases has exhibited antiglycation activity comparable to standard rutin (IC50=54.5±0.05 µM) along with a stable RMSD profile in MD simulation studies. Compound 1 also exhibited a potent α-glucosidase inhibitory activity, and moderate antioxidant property. Other derivatives showed a weak antiglycation activity with IC50 values between 248.1-637.7 µM. Compounds with potential antiglycation profile were found to be non-cytotoxic in a cellular assay. CONCLUSION The study identifies triazole Schiff's bases active against fructose-mediated glycation of HSA, thus indicates their potential against late diabetic complications due to production of advancedend products (AGEs).
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Affiliation(s)
- Muniza Shaikh
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
| | - Salman Siddiqui
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
| | - Humaira Zafar
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
| | - Uzma Naqeeb
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
| | - Fakiha Subzwari
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
| | - Rehan Imad
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
| | - Khalid M Khan
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.,Department of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Saudi Arabia
| | - Muhammad I Choudhary
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.,H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.,Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah- 21412, Saudi Arabia
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27
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Efficient Separation of Phytochemicals from Muehlenbeckia volcanica (Benth.) Endl. by Polarity-Stepwise Elution Counter-Current Chromatography and Their Antioxidant, Antiglycation, and Aldose Reductase Inhibition Potentials. Molecules 2021; 26:molecules26010224. [PMID: 33406776 PMCID: PMC7796107 DOI: 10.3390/molecules26010224] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 12/28/2020] [Accepted: 12/31/2020] [Indexed: 12/24/2022] Open
Abstract
Muehlenbeckia volcanica (Benth.) Endl. (M. volcanica), native to South America, is a traditional Peruvian medicinal plant that has multi-therapeutic properties; however, no phytochemicals have been identified from it yet. In this study, a five-step polarity-stepwise elution counter-current chromatography (CCC) was developed using methanol/water (1:5, v/v) as the stationary phase and different ratios of n-hexane, ethyl acetate, and n-butanol as mobile phases to separate the compounds from the 70% methanol extract of M. volcanica, by which six compounds with a wide range of polarities were separated in a single run of CCC and were identified as gallic acid, protocatechuic acid, 4,4'-dihydroxy-3,3'-imino-di-benzoic acid, rutin, quercitrin, and quercetin. Then, two compounds from the fractions of stepwise elution CCC were separated using conventional high-speed CCC, pH-zone-refining CCC, and preparative high-performance liquid chromatography, and identified as shikimic acid and miquelianin. These compounds are reported from M. volcanica for the first time. Notably, except for shikimic acid, all other compounds showed anti-diabetic potentials via antioxidant, antiglycation, and aldose reductase inhibition. The results suggest that the polarity-stepwise elution CCC can be used to efficiently separate or fractionate compounds with a wide range of polarities from natural products. Moreover, M. volcanica and its bioactive compounds are potent anti-diabetic agents.
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28
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Babel RA, Dandekar MP. A Review on Cellular and Molecular Mechanisms Linked to the Development of Diabetes Complications. Curr Diabetes Rev 2021; 17:457-473. [PMID: 33143626 DOI: 10.2174/1573399816666201103143818] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 10/08/2020] [Accepted: 10/12/2020] [Indexed: 11/22/2022]
Abstract
Modern lifestyle, changing eating habits and reduced physical work have been known to culminate into making diabetes a global pandemic. Hyperglycemia during the course of diabetes is an important causative factor for the development of both microvascular (retinopathy, nephropathy and neuropathy) and macrovascular (coronary artery disease, stroke and peripheral artery disease) complications. In this article, we summarize several mechanisms accountable for the development of both microvascular and macrovascular complications of diabetes. Several metabolic and cellular events are linked to the augmentation of oxidative stress like the activation of advanced glycation end products (AGE) pathway, polyol pathway, Protein Kinase C (PKC) pathway, Poly-ADP Ribose Polymerase (PARP) and hexosamine pathway. Oxidative stress also leads to the production of reactive oxygen species (ROS) like hydroxyl radical, superoxide anion and peroxides. Enhanced levels of ROS rescind the anti-oxidant defence mechanisms associated with superoxide dismutase, glutathione and ascorbic acid. Moreover, ROS triggers oxidative damages at the level of DNA, protein and lipids, which eventually cause cell necrosis or apoptosis. These physiological insults may be related to the microvascular complications of diabetes by negatively impacting the eyes, kidneys and the brain. While underlying pathomechanism of the macrovascular complications is quite complex, hyperglycemia associated atherosclerotic abnormalities like changes in the coagulation system, thrombin formation, fibrinolysis, platelet and endothelial function and vascular smooth muscle are well proven. Since hyperglycemia also modulates the vascular inflammation, cytokines, macrophage activation and gene expression of growth factors, elevated blood glucose level may play a central role in the development of macrovascular complications of diabetes. Taken collectively, chronic hyperglycemia and increased production of ROS are the miscreants for the development of microvascular and macrovascular complications of diabetes.
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Affiliation(s)
- Rishabh A Babel
- Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
| | - Manoj P Dandekar
- Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, Telangana, India
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29
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Sweet but Bitter: Focus on Fructose Impact on Brain Function in Rodent Models. Nutrients 2020; 13:nu13010001. [PMID: 33374894 PMCID: PMC7821920 DOI: 10.3390/nu13010001] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 12/11/2020] [Accepted: 12/17/2020] [Indexed: 12/13/2022] Open
Abstract
Fructose consumption has drastically increased during the last decades due to the extensive commercial use of high-fructose corn syrup as a sweetener for beverages, snacks and baked goods. Fructose overconsumption is known to induce obesity, dyslipidemia, insulin resistance and inflammation, and its metabolism is considered partially responsible for its role in several metabolic diseases. Indeed, the primary metabolites and by-products of gut and hepatic fructolysis may impair the functions of extrahepatic tissues and organs. However, fructose itself causes an adenosine triphosphate (ATP) depletion that triggers inflammation and oxidative stress. Many studies have dealt with the effects of this sugar on various organs, while the impact of fructose on brain function is, to date, less explored, despite the relevance of this issue. Notably, fructose transporters and fructose metabolizing enzymes are present in brain cells. In addition, it has emerged that fructose consumption, even in the short term, can adversely influence brain health by promoting neuroinflammation, brain mitochondrial dysfunction and oxidative stress, as well as insulin resistance. Fructose influence on synaptic plasticity and cognition, with a major impact on critical regions for learning and memory, was also reported. In this review, we discuss emerging data about fructose effects on brain health in rodent models, with special reference to the regulation of food intake, inflammation, mitochondrial function and oxidative stress, insulin signaling and cognitive function.
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30
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Effect of Fructose and Ascorbic Acid on the Performance of Cross-Linked Fish Gelatin Films. Polymers (Basel) 2020; 12:polym12030570. [PMID: 32143479 PMCID: PMC7182800 DOI: 10.3390/polym12030570] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2020] [Revised: 02/22/2020] [Accepted: 02/28/2020] [Indexed: 11/16/2022] Open
Abstract
Gelatin was extracted from fish scales in this work, in an attempt to valorise abundant and available fishery by-products as an approach towards a more circular economy. With this strategy in mind, fish scale gelatin was used to prepare active films. In this regard, the development of advanced materials from gelatin involves its modification to enhance functional properties, particularly barrier properties, to achieve the requirements for specific value-added purposes, such as food or pharmaceutical/biomedical applications. The improvement of those functional properties can be achieved by means of chemical cross-linking processes. In this context, non-enzymatic reactions were carried out with the addition of fructose and ascorbic acid into gelatin film forming formulations, and cross-linking was induced by a heat-treatment. These cross-linking reactions resulted in higher barrier features, especially for those films prepared with ascorbic acid.
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31
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Fernandes ACF, Martins IM, Moreira DKT, Macedo GA. Use of agro‐industrial residues as potent antioxidant, antiglycation agents, and α‐amylase and pancreatic lipase inhibitory activity. J FOOD PROCESS PRES 2020. [DOI: 10.1111/jfpp.14397] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
| | - Isabela Mateus Martins
- Bioprocesses Laboratory Faculty of Food Engineering University of Campinas Campinas Brazil
| | | | - Gabriela Alves Macedo
- Bioprocesses Laboratory Faculty of Food Engineering University of Campinas Campinas Brazil
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32
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Rahmanifar E, Miroliaei M. Differential effect of biophenols on attenuation of AGE-induced hemoglobin aggregation. Int J Biol Macromol 2020; 151:797-805. [PMID: 32061846 DOI: 10.1016/j.ijbiomac.2020.02.127] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2019] [Revised: 02/10/2020] [Accepted: 02/12/2020] [Indexed: 02/06/2023]
Abstract
Despite most studied activities of natural biophenols rely on antioxidant properties, little clues explored their key structural components with regard to opposing action on glycation-induced aggregation. Herein, human hemoglobin (hHb)/fructose system used to decipher if structural peculiarities of two biophenols "chlorogenic acid (CGA) and curcumin (CUR)" are effective toward AGEs-bridged aggregate formation. Suppression in amyloid cross-β formation was monitored by CD spectroscopy, fluorescence microscopy, ANS and AGE fluorescence. Reduction in molten globule structure of modified-Hb by CGA was corroborated with helix structure, thiol group and lysine residues content estimation for native, glycated and biophenols treated samples. ThT and Congo red assays showed the cross-β breaking properties of CGA. Molecular docking outcomes revealed the positioning of CGA/CUR is driven by "aromatic interactions" with Trp β1180 and Tyr α2540. These interactions are modulated by the structural constraints such as number of hydroxyl groups and their methylation status directing the biophenols to the amyloidogenic core. The results are applicable to formulation of small-molecule nutraceuticals for treatment of conformational diseases.
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Affiliation(s)
- Esmat Rahmanifar
- Department of Biology, Noordanesh Institute of Higher Education, Meymeh, Isfahan, Iran
| | - Mehran Miroliaei
- Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Iran.
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33
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The correlation between ROS generation and LPO process as the function of methylparaben concentrations during hemoglobin fructation. JOURNAL OF THE IRANIAN CHEMICAL SOCIETY 2020. [DOI: 10.1007/s13738-020-01852-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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34
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Schalkwijk CG, Stehouwer CDA. Methylglyoxal, a Highly Reactive Dicarbonyl Compound, in Diabetes, Its Vascular Complications, and Other Age-Related Diseases. Physiol Rev 2020; 100:407-461. [DOI: 10.1152/physrev.00001.2019] [Citation(s) in RCA: 370] [Impact Index Per Article: 74.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The formation and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl compound, has been implicated in the pathogenesis of type 2 diabetes, vascular complications of diabetes, and several other age-related chronic inflammatory diseases such as cardiovascular disease, cancer, and disorders of the central nervous system. MGO is mainly formed as a byproduct of glycolysis and, under physiological circumstances, detoxified by the glyoxalase system. MGO is the major precursor of nonenzymatic glycation of proteins and DNA, subsequently leading to the formation of advanced glycation end products (AGEs). MGO and MGO-derived AGEs can impact on organs and tissues affecting their functions and structure. In this review we summarize the formation of MGO, the detoxification of MGO by the glyoxalase system, and the biochemical pathways through which MGO is linked to the development of diabetes, vascular complications of diabetes, and other age-related diseases. Although interventions to treat MGO-associated complications are not yet available in the clinical setting, several strategies to lower MGO have been developed over the years. We will summarize several new directions to target MGO stress including glyoxalase inducers and MGO scavengers. Targeting MGO burden may provide new therapeutic applications to mitigate diseases in which MGO plays a crucial role.
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Affiliation(s)
- C. G. Schalkwijk
- CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands; and Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - C. D. A. Stehouwer
- CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, The Netherlands; and Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands
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35
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Siddiqui Z, Faisal M, Alatar AR, Ahmad S. Prevalence of auto-antibodies against D-ribose-glycated-hemoglobin in diabetes mellitus. Glycobiology 2019; 29:409-418. [PMID: 30834437 DOI: 10.1093/glycob/cwz012] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 02/25/2019] [Accepted: 02/28/2019] [Indexed: 01/01/2023] Open
Abstract
Glycation of biological macromolecules, due to hyperglycemia, promotes the formation of advanced glycation end products (AGEs). It is accelerated in diabetic patients and is responsible for the pathophysiology and progression of diabetes. Previous reports have shown that amount of AGEs formation and glycation-induced structural damage is higher in hemoglobin (Hb) than other proteins present in blood. In our previous study, we have shown structural changes in Hb by D-ribose which may result into the generation of immunogenic neo-epitopes. Thus, we hypothesized that D-ribose induced structural perturbations in Hb, could result in the formation of neo-epitopes which may provoke an auto-immune response and may also be involved in the immuno-pathogenesis of diabetes type-2 associated complications. Therefore, in the current study, we analyzed the prevalence of autoantibodies in diabetic patient's sera against D-ribose glycated-Hb by direct binding and competitive ELISA. Direct binding ELISA confirmed that autoantibodies in diabetic patients exhibit significantly high binding with D-ribose glycated-Hb as compared to its native form. The antigen binding specificity of these antibodies was also screened by competitive inhibition ELISA. We also used D-glucose glycated-Hb as a positive control to detect the presence of auto-antibodies by direct binding and inhibiton ELISA. We found that D-glucose glycated-Hb binds with T2DM samples but the affinity to binding is lower than D-ribose glycated-Hb. The overall findings of this study suggest the prevalence of circulating autoantibodies against D-ribose glycated-Hb in diabetic patients and thus, the level of these autoantibodies may be used as biomarker for progression of diabetes.
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Affiliation(s)
- Zeba Siddiqui
- Department of Biosciences, Integral University, Lucknow, India.,IIRC-1 Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India
| | - Mohammad Faisal
- Department of Botany & Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Abdul Rahman Alatar
- Department of Botany & Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia
| | - Saheem Ahmad
- Department of Biosciences, Integral University, Lucknow, India.,IIRC-1 Laboratory of Glycation Biology and Metabolic Disorders, Integral University, Lucknow, India
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Pacholko AG, Wotton CA, Bekar LK. Poor Diet, Stress, and Inactivity Converge to Form a "Perfect Storm" That Drives Alzheimer's Disease Pathogenesis. NEURODEGENER DIS 2019; 19:60-77. [PMID: 31600762 DOI: 10.1159/000503451] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 09/17/2019] [Indexed: 11/19/2022] Open
Abstract
North American incidence of Alzheimer's disease (AD) is expected to more than double over the coming generation. Although genetic factors surrounding the production and clearance of amyloid-β and phosphorylated tau proteins are known to be responsible for a subset of early-onset AD cases, they do not explain the pathogenesis of the far more prevalent sporadic late-onset variant of the disease. It is thus likely that lifestyle and environmental factors contribute to neurodegenerative processes implicated in the pathogenesis of AD. Herein, we review evidence that (1) excess sucrose consumption induces AD-associated liver pathologies and brain insulin resistance, (2) chronic stress overdrives activity of locus coeruleus neurons, leading to loss of function (a common event in neurodegeneration), (3) high-sugar diets and stress promote the loss of neuroprotective sex hormones in men and women, and (4) Western dietary trends set the stage for a lithium-deficient state. We propose that these factors may intersect as part of a "perfect storm" to contribute to the widespread prevalence of neurodegeneration and AD. In addition, we put forth the argument that exercise and supplementation with trace lithium can counteract many of the deleterious consequences associated with excessive caloric intake and perpetual stress. We conclude that lifestyle and environmental factors likely contribute to AD pathogenesis and that simple lifestyle and dietary changes can help counteract their effects.
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Affiliation(s)
- Anthony G Pacholko
- Department of Anatomy, Physiology, and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Caitlin A Wotton
- Department of Anatomy, Physiology, and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Lane K Bekar
- Department of Anatomy, Physiology, and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada,
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Rai AK, Singh SP, Pandey AR, Ansari A, Ahmad S, Sashidhara KV, Tamrakar AK. Flavonoids from Polyalthia longifolia prevents advanced glycation end products formation and protein oxidation aligned with fructose-induced protein glycation. Nat Prod Res 2019; 35:2921-2925. [PMID: 31583901 DOI: 10.1080/14786419.2019.1672690] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Advanced glycation end products (AGEs) are reactive chemical entities formed by non-enzymatic reaction between reducing sugars and amino group of proteins. Enhanced accumulation of AGEs and associated protein oxidation contribute to pathogenesis of diabetes-associated complications. Here, we evaluated the inhibitory activity of flavonoid compounds isolated from the leaves of Polyalthia longifolia on formation of AGEs and protein oxidation. Antiglycation activity was determined by measuring the formation of AGE fluorescence intensity, Nε-(carboxymethyl) lysine, and level of fructosamine. Protein oxidation was examined using levels of protein carbonyls and thiol group. Compounds significantly (p < 0.001) restricted the formation of fluorescent AGEs in fructose- BSA and methylglyoxal-BSA systems. Furthermore, there was a decrease in levels of fructosamine and protein carbonyls, and elevation in level of thiol group in fructose-BSA in presence of flavonoids. In summary, flavonoids from Polyalthia longifolia inhibit fructose-mediated protein glycation and oxidation, and can be potential agent for preventing AGE-mediated diabetic complications.
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Affiliation(s)
- Amit K Rai
- Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow, India
| | - Suriya P Singh
- Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, India
| | - Alka Raj Pandey
- Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, India
| | - Alisha Ansari
- Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, India
| | - Shadab Ahmad
- Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow, India.,Academy of Scientific and Innovative Research (AcSIR), New Delhi, India
| | - Koneni V Sashidhara
- Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow, India
| | - Akhilesh K Tamrakar
- Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow, India.,Academy of Scientific and Innovative Research (AcSIR), New Delhi, India
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Wang Y, Wang L, Xu G, Wei D. Hesperidin Exerts the Gestational Diabetes Mellitus via AGEs-RAGE Signalling Pathway. INT J PHARMACOL 2019. [DOI: 10.3923/ijp.2019.604.615] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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39
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Rai AK, Jaiswal N, Maurya CK, Sharma A, Ahmad I, Ahmad S, Gupta AP, Gayen JR, Tamrakar AK. Fructose-induced AGEs-RAGE signaling in skeletal muscle contributes to impairment of glucose homeostasis. J Nutr Biochem 2019; 71:35-44. [PMID: 31272030 DOI: 10.1016/j.jnutbio.2019.05.016] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Revised: 05/22/2019] [Accepted: 05/24/2019] [Indexed: 02/06/2023]
Abstract
Increased fructose intake has been linked to the development of dyslipidemia, obesity and impaired glucose tolerance. Due to its specific metabolic fate, fructose impairs normal lipid and carbohydrate metabolism and facilitates the non-enzymatic glycation reaction leading to enhanced accumulation of advanced glycation end products (AGEs). However, the formation of fructose-AGEs under in vivo setup and its tissue specific accumulation is less explored. Here, we investigated the impact of high fructose on AGEs accumulation in skeletal muscle and its causal role in impaired glucose homeostasis. In L6 rat skeletal muscle cells, chronic exposure to fructose induced AGEs accumulation and the cellular level of the receptor for AGEs (RAGE) and the effect was prevented by pharmacological inhibition of glycation. Under in vivo settings, Sprague Dawley rats exposed to 20% fructose in drinking water for 16 weeks, displayed increased fasting glycemia, impaired glucose tolerance, decreased skeletal muscle Akt (Ser-473) phosphorylation, and enhanced triglyceride levels in serum, liver and gastrocnemius muscle. We also observed a high level of AGEs in serum and gastrocnemius muscle of fructose-supplemented animals, associated with methylglyoxal accumulation and up regulated expression of RAGE in gastrocnemius muscle. Treatment with aminoguanidine inhibited fructose-induced AGEs accumulation and normalized the expression of RAGE and Dolichyl-Diphosphooligosaccharide-Protein Glycosyltransferase (DDOST) in gastrocnemius muscle. Inhibition of AGEs-RAGE axis counteracted fructose-mediated glucose intolerance without affecting energy metabolism. These data reveal diet-derived AGEs accumulation in skeletal muscle and the implication of tissue specific AGEs in metabolic derangement, that may open new perspectives in pathogenic mechanisms and management of metabolic diseases.
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Affiliation(s)
- Amit K Rai
- Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow-226031
| | - Natasha Jaiswal
- Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow-226031
| | - Chandan K Maurya
- Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow-226031
| | - Aditya Sharma
- Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow-226031
| | - Ishbal Ahmad
- Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow-226031
| | - Shadab Ahmad
- Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow-226031; Academy of Scientific and Innovative Research (AcSIR), New Delhi-201002, India
| | - Anand P Gupta
- Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow-226031
| | - Jiaur R Gayen
- Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow-226031
| | - Akhilesh K Tamrakar
- Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow-226031; Academy of Scientific and Innovative Research (AcSIR), New Delhi-201002, India.
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Ghazanfari-Sarabi S, Habibi-Rezaei M, Eshraghi-Naeeni R, Moosavi-Movahedi AA. Prevention of haemoglobin glycation by acetylsalicylic acid (ASA): A new view on old mechanism. PLoS One 2019; 14:e0214725. [PMID: 30986221 PMCID: PMC6464172 DOI: 10.1371/journal.pone.0214725] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Accepted: 03/19/2019] [Indexed: 01/10/2023] Open
Abstract
Diabetic hyperglycemia provokes glycation of haemoglobin (Hb), an abundant protein in red blood cells (RBCs), by increasing its exposure to carbohydrates. Acetylsalicylic acid (ASA; Aspirin) is one of the first agents, which its antiglycation effect was witnessed. Although the precise molecular mechanism of action of ASA on protein glycation is not indisputably perceived, acetylation as its main molecular mechanism has been proposed. This report aims to unravel the meticulous mechanism of action of ASA by using two ASA analogues; benzoic acid (BA) and para-nitrobenzoic acid (NBA), despite their lack of acetyl group. In this regard, the inhibitory effect of these two chemicals in comparison with ASA on Hb fructation is reported. UV-visible spectroscopy, intrinsic advanced glycation end products (AGE) fluorescence spectroscopy, extrinsic thioflavin T (ThT) binding fluorescence spectroscopy, 2,4,6-trinitrobenzenesulfonic acid (TNBSA) assay, and single cell gel electrophoresis (SCGE) were used to explore the effects of BA and NBA in comparison with aforementioned chemicals in the context of protein glycation. In spite of the lack of acetyl substitution, NBA is reported as a novel agent with prominent inhibitory efficacy than ASA on the protein glycation. This fact brings up a possible new mechanism of action of ASA and reconsiders acetylation as the sole mechanism of inhibition of protein glycation.
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Affiliation(s)
| | - Mehran Habibi-Rezaei
- School of Biology, College of Science, University of Tehran, Tehran, Iran
- Nano-Biomedicine Center of Excellence, Nanoscience and Nanotechnology Research Center, University of Tehran, Tehran, Iran
- * E-mail:
| | | | - Ali Akbar Moosavi-Movahedi
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
- Center of Excellence in Biothermodynamics, University of Tehran, Tehran, Iran
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Todhunter ME, Sayaman RW, Miyano M, LaBarge MA. Tissue aging: the integration of collective and variant responses of cells to entropic forces over time. Curr Opin Cell Biol 2018; 54:121-129. [PMID: 29908481 PMCID: PMC6258070 DOI: 10.1016/j.ceb.2018.05.016] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Revised: 04/13/2018] [Accepted: 05/30/2018] [Indexed: 01/08/2023]
Abstract
Aging is driven by unavoidable entropic forces, physicochemical in nature, that damage the raw materials that constitute biological systems. Single cells experience and respond to stochastic physicochemical insults that occur either to the cells themselves or to their microenvironment, in a dynamic and reciprocal manner, leading to increased age-related cell-to-cell variation. We will discuss the biological mechanisms that integrate cell-to-cell variation across tissues resulting in stereotypical phenotypes of age.
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Affiliation(s)
- Michael E Todhunter
- Department of Populations Sciences, and Center for Cancer and Aging, Beckman Research Institute at City of Hope, 1500 E Duarte Rd, Duarte, CA 91011 USA
| | - Rosalyn W Sayaman
- Department of Populations Sciences, and Center for Cancer and Aging, Beckman Research Institute at City of Hope, 1500 E Duarte Rd, Duarte, CA 91011 USA
| | - Masaru Miyano
- Department of Populations Sciences, and Center for Cancer and Aging, Beckman Research Institute at City of Hope, 1500 E Duarte Rd, Duarte, CA 91011 USA
| | - Mark A LaBarge
- Department of Populations Sciences, and Center for Cancer and Aging, Beckman Research Institute at City of Hope, 1500 E Duarte Rd, Duarte, CA 91011 USA.
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Habitual Fructose Intake Relates to Insulin Sensitivity and Fatty Liver Index in Recent-Onset Type 2 Diabetes Patients and Individuals without Diabetes. Nutrients 2018; 10:nu10060774. [PMID: 29914103 PMCID: PMC6024554 DOI: 10.3390/nu10060774] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 06/07/2018] [Accepted: 06/13/2018] [Indexed: 12/16/2022] Open
Abstract
The association between the amount and sources of fructose intake with insulin sensitivity and liver fat needs further elucidation. This study aimed at examining whether habitual intake of sucrose plus non-sucrose bound as well as of non-sucrose bound fructose (total fructose, fruit-derived, juice-derived, sugar sweetened beverages (SSB)-derived fructose) is cross-sectionally associated with insulin sensitivity and fatty liver index (FLI). Fructose intake was estimated using the EPIC food frequency questionnaire from 161 participants with type 2 diabetes (T2D) in the ongoing German Diabetes Study (GDS) (age 53 ± 9 years; HbA1c 6.4 ± 0.9%) and 62 individuals without diabetes (CON) (47 ± 14 years; 5.3 ± 0.3%). Peripheral (M-value) and hepatic insulin resistance were assessed by hyperinsulinemic-euglycemic clamps with stable isotope dilution. FLI was calculated based on body mass index, waist circumference, triglyceride and gamma glutamyl transferase concentrations. Multivariable linear regression analyses were performed. A doubling of SSB-derived sucrose plus non-sucrose bound as well as of non-sucrose bound fructose intake was independently associated with a reduction of the M-value by −2.6% (−4.9; −0.2) and −2.7% (−5.2; −0.1) among T2D, respectively, with an increase in the odds of fatty liver by 16% and 17%, respectively among T2D (all p < 0.05). Doubling fruit-derived sucrose plus non-sucrose bound fructose intake independently related to a reduction in the odds of fatty liver by 13% (p = 0.033) among T2D. Moderate SSB-derived fructose intake may detrimentally affect peripheral insulin sensitivity, whereas fruit-derived fructose intake appeared beneficial for liver fat content.
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Abstract
Increased understanding of fructose metabolism, which begins with uptake via the intestine, is important because fructose now constitutes a physiologically significant portion of human diets and is associated with increased incidence of certain cancers and metabolic diseases. New insights in our knowledge of intestinal fructose absorption mediated by the facilitative glucose transporter GLUT5 in the apical membrane and by GLUT2 in the basolateral membrane are reviewed. We begin with studies related to structure as well as ligand binding, then revisit the controversial proposition that apical GLUT2 is the main mediator of intestinal fructose absorption. The review then describes how dietary fructose may be sensed by intestinal cells to affect the expression and activity of transporters and fructolytic enzymes, to interact with the transport of certain minerals and electrolytes, and to regulate portal and peripheral fructosemia and glycemia. Finally, it discusses the potential contributions of dietary fructose to gastrointestinal diseases and to the gut microbiome.
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Affiliation(s)
- Ronaldo P Ferraris
- Department of Pharmacology, Physiology and Neuroscience, New Jersey Medical School, Rutgers University, Newark, New Jersey 07946, USA;
| | - Jun-Yong Choe
- Department of Biochemistry and Molecular Biology, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, North Chicago, Illinois 60064, USA;
| | - Chirag R Patel
- Independent Drug Safety Consulting, Wilmington, Delaware 19803, USA;
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44
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Gliemann L, Rytter N, Lindskrog M, Slingsby MHL, Åkerström T, Sylow L, Richter EA, Hellsten Y. Endothelial mechanotransduction proteins and vascular function are altered by dietary sucrose supplementation in healthy young male subjects. J Physiol 2018. [PMID: 28620941 DOI: 10.1113/jp274623] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
KEY POINTS Mechanotransduction in endothelial cells is a central mechanism in the regulation of vascular tone and vascular remodelling Mechanotransduction and vascular function may be affected by high sugar levels in plasma because of a resulting increase in oxidative stress and increased levels of advanced glycation end-products (AGE). In healthy young subjects, 2 weeks of daily supplementation with 3 × 75 g of sucrose was found to reduce blood flow in response to passive lower leg movement and in response to 12 W of knee extensor exercise. This vascular impairment was paralleled by up-regulation of platelet endothelial cell adhesion molecule (PECAM)-1, endothelial nitric oxide synthase, NADPH oxidase and Rho family GTPase Rac1 protein expression, an increased basal phosphorylation status of vascular endothelial growth factor receptor 2 and a reduced phosphorylation status of PECAM-1. There were no measurable changes in AGE levels. The findings of the present study demonstrate that daily high sucrose intake markedly affects mechanotransduction proteins and has a detrimental effect on vascular function. ABSTRACT Endothelial mechanotransduction is important for vascular function but alterations and activation of vascular mechanosensory proteins have not been investigated in humans. In endothelial cell culture, simple sugars effectively impair mechanosensor proteins. To study mechanosensor- and vascular function in humans, 12 young healthy male subjects supplemented their diet with 3 × 75 g sucrose day-1 for 14 days in a randomized cross-over design. Before and after the intervention period, the hyperaemic response to passive lower leg movement and active knee extensor exercise was determined by ultrasound doppler. A muscle biopsy was obtained from the thigh muscle before and after acute passive leg movement to allow assessment of protein amounts and the phosphorylation status of mechanosensory proteins and NADPH oxidase. The sucrose intervention led to a reduced flow response to passive movement (by 17 ± 2%) and to 12 W of active exercise (by 9 ± 1%), indicating impaired vascular function. A reduced flow response to passive and active exercise was paralleled by a significant up-regulation of platelet endothelial cell adhesion molecule (PECAM-1), endothelial nitric oxide synthase, NADPH oxidase and the Rho family GTPase Rac1 protein expression in the muscle tissue, as well as an increased basal phosphorylation status of vascular endothelial growth factor receptor 2 and a reduced phosphorylation status of PECAM-1. The phosphorylation status was not acutely altered with passive leg movement. These findings indicate that a regular intake of high levels of sucrose can impair vascular mechanotransduction and increase the oxidative stress potential, and suggest that dietary excessive sugar intake may contribute to the development of vascular disease.
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Affiliation(s)
- Lasse Gliemann
- Section for Integrative Physiology, University of Copenhagen, Copenhagen, Denmark
| | - Nicolai Rytter
- Section for Integrative Physiology, University of Copenhagen, Copenhagen, Denmark
| | - Mads Lindskrog
- Section for Integrative Physiology, University of Copenhagen, Copenhagen, Denmark
| | | | - Thorbjörn Åkerström
- Section for Integrative Physiology, University of Copenhagen, Copenhagen, Denmark.,Insulin Pharmacology Department, Novo Nordisk A/S, Maaloev, Denmark
| | - Lykke Sylow
- Section Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
| | - Erik A Richter
- Section Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
| | - Ylva Hellsten
- Section for Integrative Physiology, University of Copenhagen, Copenhagen, Denmark
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Metabolic shift from glycogen to trehalose promotes lifespan and healthspan in Caenorhabditis elegans. Proc Natl Acad Sci U S A 2018; 115:E2791-E2800. [PMID: 29511104 DOI: 10.1073/pnas.1714178115] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
As Western diets continue to include an ever-increasing amount of sugar, there has been a rise in obesity and type 2 diabetes. To avoid metabolic diseases, the body must maintain proper metabolism, even on a high-sugar diet. In both humans and Caenorhabditis elegans, excess sugar (glucose) is stored as glycogen. Here, we find that animals increased stored glycogen as they aged, whereas even young adult animals had increased stored glycogen on a high-sugar diet. Decreasing the amount of glycogen storage by modulating the C. elegans glycogen synthase, gsy-1, a key enzyme in glycogen synthesis, can extend lifespan, prolong healthspan, and limit the detrimental effects of a high-sugar diet. Importantly, limiting glycogen storage leads to a metabolic shift whereby glucose is now stored as trehalose. Two additional means to increase trehalose show similar longevity extension. Increased trehalose is entirely dependent on a functional FOXO transcription factor DAF-16 and autophagy to promote lifespan and healthspan extension. Our results reveal that when glucose is stored as glycogen, it is detrimental, whereas, when stored as trehalose, animals live a longer, healthier life if DAF-16 is functional. Taken together, these results demonstrate that trehalose modulation may be an avenue for combatting high-sugar-diet pathology.
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Mastrocola R, Ferrocino I, Liberto E, Chiazza F, Cento AS, Collotta D, Querio G, Nigro D, Bitonto V, Cutrin JC, Rantsiou K, Durante M, Masini E, Aragno M, Cordero C, Cocolin L, Collino M. Fructose liquid and solid formulations differently affect gut integrity, microbiota composition and related liver toxicity: a comparative in vivo study. J Nutr Biochem 2018. [PMID: 29539590 DOI: 10.1016/j.jnutbio.2018.02.003] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Despite clinical findings suggesting that the form (liquid versus solid) of the sugars may significantly affect the development of metabolic diseases, no experimental data are available on the impact of their formulations on gut microbiota, integrity and hepatic outcomes. In the present sudy, C57Bl/6j mice were fed a standard diet plus water (SD), a standard diet plus 60% fructose syrup (L-Fr) or a 60% fructose solid diet plus water (S-Fr) for 12 weeks. Gut microbiota was characterized through 16S rRNA phylogenetic profiling and shotgun sequencing of microbial genes in ileum content and related volatilome profiling. Fructose feeding led to alterations of the gut microbiota depending on the fructose formulation, with increased colonization by Clostridium, Oscillospira and Clostridiales phyla in the S-Fr group and Bacteroides, Lactobacillus, Lachnospiraceae and Dorea in the L-Fr. S-Fr evoked the highest accumulation of advanced glycation end products and barrier injury in the ileum intestinal mucosa. These effects were associated to a stronger activation of the lipopolysaccharide-dependent proinflammatory TLR4/NLRP3 inflammasome pathway in the liver of S-Fr mice than of L-Fr mice. In contrast, L-Fr intake induced higher levels of hepatosteatosis and markers of fibrosis than S-Fr. Fructose-induced ex novo lipogenesis with production of SCFA and MCFA was confirmed by metagenomic analysis. These results suggest that consumption of fructose under different forms, liquid or solid, may differently affect gut microbiota, thus leading to impairment in intestinal mucosa integrity and liver homeostasis.
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Affiliation(s)
- Raffaella Mastrocola
- Dept. of Clinical and Biological Sciences, University of Turin, Italy; Dept. Internal Medicine, University of Maastricht, The Netherlands
| | - Ilario Ferrocino
- Dept. of Agricultural, Forest and Food Sciences, University of Turin, Italy
| | - Erica Liberto
- Dept. of Drug Science and Technology, University of Turin, Italy
| | - Fausto Chiazza
- Dept. of Drug Science and Technology, University of Turin, Italy
| | | | - Debora Collotta
- Dept. of Drug Science and Technology, University of Turin, Italy
| | - Giulia Querio
- Dept. of Drug Science and Technology, University of Turin, Italy
| | - Debora Nigro
- Dept. of Clinical and Biological Sciences, University of Turin, Italy
| | - Valeria Bitonto
- Dept. of Molecular Biotechnology and Sciences for the Health, University of Turin, Italy
| | - Juan Carlos Cutrin
- Dept. of Molecular Biotechnology and Sciences for the Health, University of Turin, Italy
| | - Kalliopi Rantsiou
- Dept. of Agricultural, Forest and Food Sciences, University of Turin, Italy
| | - Mariaconcetta Durante
- Dept. of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy
| | - Emanuela Masini
- Dept. of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Italy
| | - Manuela Aragno
- Dept. of Clinical and Biological Sciences, University of Turin, Italy
| | - Chiara Cordero
- Dept. of Drug Science and Technology, University of Turin, Italy
| | - Luca Cocolin
- Dept. of Agricultural, Forest and Food Sciences, University of Turin, Italy.
| | - Massimo Collino
- Dept. of Drug Science and Technology, University of Turin, Italy.
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Maciążek-Jurczyk M, Szkudlarek A, Chudzik M, Pożycka J, Sułkowska A. Alteration of human serum albumin binding properties induced by modifications: A review. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2018; 188:675-683. [PMID: 28526195 DOI: 10.1016/j.saa.2017.05.023] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Revised: 04/23/2017] [Accepted: 05/09/2017] [Indexed: 06/07/2023]
Abstract
Albumin, a major transporting protein in the blood, is the main target of modification that affects the binding of drugs to Sudlow's site I and II. These modification of serum protein moderates its physiological function, and works as a biomarker of some diseases. The main goal of the paper was to explain the possible alteration of human serum albumin binding properties induced by modifications such as glycation, oxidation and ageing, their origin, methods of evaluation and positive and negative meaning described by significant researchers.
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Affiliation(s)
- Małgorzata Maciążek-Jurczyk
- School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Chair and Department of Physical Pharmacy, Jagiellońska 4, 41-200 Sosnowiec, Poland.
| | - Agnieszka Szkudlarek
- School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Chair and Department of Physical Pharmacy, Jagiellońska 4, 41-200 Sosnowiec, Poland
| | - Mariola Chudzik
- School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Chair and Department of Physical Pharmacy, Jagiellońska 4, 41-200 Sosnowiec, Poland
| | - Jadwiga Pożycka
- School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Chair and Department of Physical Pharmacy, Jagiellońska 4, 41-200 Sosnowiec, Poland
| | - Anna Sułkowska
- Silesian Medical College in Katowice, Mickiewicza 29, 40-085 Katowice, Poland
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48
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Chang KC, Petrash JM. Aldo-Keto Reductases: Multifunctional Proteins as Therapeutic Targets in Diabetes and Inflammatory Disease. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1032:173-202. [PMID: 30362099 DOI: 10.1007/978-3-319-98788-0_13] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Aldose reductase (AR) is an NADPH-dependent aldo-keto reductase that has been shown to be involved in the pathogenesis of several blinding diseases such as uveitis, diabetic retinopathy (DR) and cataract. However, possible mechanisms linking the action of AR to these diseases are not well understood. As DR and cataract are among the leading causes of blindness in the world, there is an urgent need to explore therapeutic strategies to prevent or delay their onset. Studies with AR inhibitors and gene-targeted mice have demonstrated that the action of AR is also linked to cancer onset and progression. In this review we examine possible mechanisms that relate AR to molecular signaling cascades and thus explain why AR inhibition is an effective strategy against colon cancer as well as diseases of the eye such as uveitis, cataract, and retinopathy.
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Affiliation(s)
- Kun-Che Chang
- Department of Ophthalmology, School of Medicine, University of Colorado, Aurora, CO, USA.,Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA
| | - J Mark Petrash
- Department of Ophthalmology, School of Medicine, University of Colorado, Aurora, CO, USA. .,Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA.
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49
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da Luz PL, Favarato D, Berwanger O. Action of Red Wine and Polyphenols Upon Endothelial Function and Clinical Events. ENDOTHELIUM AND CARDIOVASCULAR DISEASES 2018:391-418. [DOI: 10.1016/b978-0-12-812348-5.00026-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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50
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Abstract
The extracellular matrix (ECM) provides the environment for many cells types within the body and, in addition to the well recognised role as a structural support, influences many important cell process within the body. As a result, age-related changes to the proteins of the ECM have far reaching consequences with the potential to disrupt many different aspects of homeostasis and healthy function. The proteins collagen and elastin are the most abundant in the ECM and their ability to function as a structural support and provide mechanical stability results from the formation of supra-molecular structures. Collagen and elastin have a long half-life, as required by their structural role, which leaves them vulnerable to a range of post-translational modifications. In this chapter the role of the ECM is discussed and the component proteins introduced. Major age-related modifications including glycation, carbamylation and fragmentation and the impact these have on ECM function are reviewed.
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