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Shang D, Zhao S. Molecular mechanisms of obesity predisposes to atopic dermatitis. Front Immunol 2024; 15:1473105. [PMID: 39564133 PMCID: PMC11574713 DOI: 10.3389/fimmu.2024.1473105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Accepted: 10/15/2024] [Indexed: 11/21/2024] Open
Abstract
Obesity is a prevalent metabolic disease that reduces bacterial diversity, colonizes the epidermis with lipophilic bacteria, and increases intestinal pro-inflammatory species, all of which lead to impaired epithelial barriers. Adipose tissue secretes immunomodulatory molecules, such as adipokines, leptin, and adiponectin, which alters the morphology of adipocytes and macrophages as well as modulates T cell differentiation and peripheral Th2-dominated immune responses. Atopic dermatitis (AD) and obesity have similar pathological manifestations, including inflammation as well as insulin and leptin resistance. This review examines the major mechanisms between obesity and AD, which focus on the effect on skin and gut microbiota, immune responses mediated by the toll like receptor (TLR) signaling pathway, and changes in cytokine levels (TNF-a, IL-6, IL-4, and IL13). Moreover, we describe the potential effects of adipokines on AD and finally mechanisms by which PPAR-γ suppresses and regulates type 2 immunity.
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Affiliation(s)
- Dajin Shang
- School of China Medical University, Shenyang, Liaoning, China
| | - Shengnan Zhao
- School of China Medical University, Shenyang, Liaoning, China
- Department of Dermatology, The First Hospital of China Medical University, Shenyang, China
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Xie S, Kuang W, Guo M, Yang F, Jin H, Chen X, Yi L, Huo C, Xu Z, Lin A, Liu W, Mao J, Shu Q, Zhou T. m6Am methyltransferase PCIF1 negatively regulates ciliation by inhibiting BICD2 expression. J Cell Biol 2024; 223:e202307002. [PMID: 38526325 PMCID: PMC10965392 DOI: 10.1083/jcb.202307002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 01/07/2024] [Accepted: 02/29/2024] [Indexed: 03/26/2024] Open
Abstract
N6, 2'-O-dimethyladenosine (m6Am) is a widespread RNA modification catalyzed by the methyltransferase PCIF1 (phosphorylated CTD interacting factor 1). Despite its prevalence, the biological functions of m6Am in RNA remain largely elusive. Here, we report a critical role of PCIF1-dependent m6Am RNA modification in ciliogenesis in RPE-1 cells. Our findings demonstrate that PCIF1 acts as a negative regulator of ciliation through its m6Am methyltransferase activity. A quantitative proteomic analysis identifies BICD2 as a downstream target of PCIF1, with PCIF1 depletion resulting in a significant increase in BICD2 levels. BICD2 depletion leads to a significant reduction in ciliation. Crucially, the ciliary phenotype in PCIF1-depleted cells is reversed upon BICD2 knockdown. Further investigations reveal that PCIF1 regulates BICD2 protein levels through its m6Am catalytic activity, which reduces the stability and translation efficiency of BICD2 mRNA. Single-base resolution LC-MS analysis identifies the m6Am site on BICD2 mRNA modified by PCIF1. These findings establish the essential involvement of PCIF1-dependent m6Am modification in ciliogenesis.
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Affiliation(s)
- Shanshan Xie
- Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Wenjun Kuang
- International Institutes of Medicine, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China
| | - Mengzhe Guo
- School of Pharmacy, Xuzhou Medical University, Xuzhou, China
| | - Feng Yang
- Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Hao Jin
- Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiying Chen
- Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, China
| | - Li Yi
- Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, China
| | - Chunxiao Huo
- Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, China
| | - Zhangqi Xu
- Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Aifu Lin
- MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China
| | - Wei Liu
- Metabolic Medicine Center, International Institutes of Medicine and the Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, China
| | - Jianhua Mao
- Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Qiang Shu
- Children’s Hospital, National Clinical Research Center for Child Health, Zhejiang University School of Medicine, Hangzhou, China
| | - Tianhua Zhou
- Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, China
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An F, Meng X, Yuan L, Niu Y, Deng J, Li Z, Liu Y, Xia R, Liu S, Yan C. Network regulatory mechanism of ncRNA on the Wnt signaling pathway in osteoporosis. Cell Div 2023; 18:3. [PMID: 36879309 PMCID: PMC9990358 DOI: 10.1186/s13008-023-00086-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 01/24/2023] [Indexed: 03/08/2023] Open
Abstract
Non-coding RNA (ncRNA) is a type of non-protein-coding RNA molecule transcribed from the genome which performs broad regulation of a variety of biological functions in human cells. The Wnt signaling pathway is highly conserved in multicellular organisms, playing an important role in their growth and development. Increasing evidence suggests that ncRNA can regulate cell biological function, enhance bone metabolism, and maintain normal bone homeostasis by interacting with the Wnt pathway. Studies have also demonstrated that the association of ncRNA with the Wnt pathway may be a potential biomarker for the diagnosis, evaluation of prognosis, and treatment of osteoporosis. The interaction of ncRNA with Wnt also performs an important regulatory role in the occurrence and development of osteoporosis. Targeted therapy of the ncRNA/Wnt axis may ultimately be the preferred choice for the treatment of osteoporosis in the future. The current article reviews the mechanism of the ncRNA/Wnt axis in osteoporosis and reveals the relationship between ncRNA and Wnt, thereby exploring novel molecular targets for the treatment of osteoporosis and providing theoretical scientific guidance for its clinical treatment.
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Affiliation(s)
- Fangyu An
- Teaching Experiment Training Center, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Xiangrui Meng
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Lingqing Yuan
- School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Yanqiang Niu
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Jie Deng
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Zhaohui Li
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Yongqi Liu
- School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China.
| | - Ruoliu Xia
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Shiqing Liu
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Chunlu Yan
- School of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China.
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Shang X, Liu K, Wang Z, Sun Y, Cao N, Huang W, Zhu Y, Wang W. Screening and analysis of key genes in the biological behavior of bone mesenchymal stem cells seeded on gradient nanostructured titanium compared with native pure Ti. J Biomater Appl 2023; 37:1086-1101. [PMID: 36063429 DOI: 10.1177/08853282221125036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Titanium (Ti) and Ti-based alloy materials are ideal brackets that restore bone defect, and the mechanism of related genes inducing bone mesenchymal stem cells (BMSCs) to osteogenic differentiation is currently a hot research topic. In order to screen key genes of BMSCs during the osteogenic expression process, we acquired data sets (GSE37237 and GSE84500) which were in the database Gene Expression Omnibus (GEO). Investigations on differentially expressed genes (DEGs) and their enrichment of functions were conducted. We constructed relative protein-protein interaction (PPI) network by using Search Tool for the Retrieval of Interacting Genes (STRING) and visualized the expression of DEGs with Cytoscape. A total of 279 DEGs were discerned, which could be divided into 177 down regulated genes and 102 up regulated genes. In addition, the DEGs' enrichment and pathways included regulation of actin cytoskeleton, inflammatory mediator regulation of transient receptor potential (TRP) channels, peroxisome proliferator-activated receptors (PPAR) pathway, cell cycle, Rheumatoid arthritis, mitogen-activated protein kinases (MAPK) signaling pathway and Ras signaling pathway ect. It showed that 10 notable up regulated genes were mainly in AMP-activated protein kinase (AMPK) pathway. Then we used a technology named surface mechanical attrition treatment (SMAT) to prepare gradient nanostructured (GNS) surface Ti and seeded well-growing BMSCs on the surface of SMAT Ti and native pure Ti. Cell Counting Kits-8 (CCK-8), apoptosis experiment, immunofluorescence technology and staining experiments for alka-line phosphatase (ALP) and alizarin red staining (ARS) were used to research the proliferation, adhesion and differentiation ability of BMSCs seeded on SMAT Ti compared with native pure Ti. We used quantitative real-time PCR (qRT-PCR) technology so as to verify the expression of the most significant 5 genes. In summary, these results indicated novel point of views into candidate genes and potential mechanism for the further study of BMSCs' behaviors seeded on SMAT Ti.
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Affiliation(s)
- Xinyue Shang
- 576019General Dentistry Dep, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110001, China
| | - Keda Liu
- 576019General Dentistry Dep, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110001, China
| | - Zhenbo Wang
- 71123Metallic Nano-Materials Division, Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy Sciences, Shenyang 110016, China
| | - Yantao Sun
- 71123Metallic Nano-Materials Division, Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy Sciences, Shenyang 110016, China
| | - Nanjue Cao
- 576019General Dentistry Dep, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110001, China
| | - Wei Huang
- 576019General Dentistry Dep, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110001, China
| | - Yuhe Zhu
- 576019General Dentistry Dep, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110001, China
| | - Wei Wang
- 576019General Dentistry Dep, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, Shenyang 110001, China
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Li D, Guo J, Ni X, Sun G, Bao H. The progress and challenges of circRNA for diabetic foot ulcers: A mini-review. Front Endocrinol (Lausanne) 2022; 13:1019935. [PMID: 36531481 PMCID: PMC9747764 DOI: 10.3389/fendo.2022.1019935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Accepted: 11/14/2022] [Indexed: 12/05/2022] Open
Abstract
Since the Human Genome Project was successfully completed, humanity has entered a post-genome era, and the second-generation sequencing technology has gradually progressed and become more accurate. Meanwhile, circRNAs plays a crucial role in the regulation of diseases and potential clinical applications has gradually attracted the attention of physicians. However, the mechanisms of circRNAs regulation at the cellular and molecular level of diabetic foot ulcer (DFU) is still not well-understood. With the deepening of research, there have been many recent studies conducted to explore the effect of circRNAs on DFU. In this mini-review, we discuss the potential role of circRNAs as therapeutic targets and diagnostic markers for DFU in order to gain a better understanding of the molecular mechanisms that underlie the development of DFU and to establish a theoretical basis for accurate treatment and effective prevention.
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Affiliation(s)
- Deer Li
- Graduate School, Inner Mongolia Medical University, Hohhot, China
- Department of Traumatology and Orthopedics, Inner Mongolia People’s Hospital, Hohhot, China
| | - Jiaxing Guo
- Department of Joint Surgery, The Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot, China
| | - Xiyu Ni
- Graduate School, Inner Mongolia Medical University, Hohhot, China
- Department of Traumatology and Orthopedics, Inner Mongolia People’s Hospital, Hohhot, China
| | - Guanwen Sun
- Department of Traumatology and Orthopedics, Inner Mongolia People’s Hospital, Hohhot, China
| | - Huhe Bao
- Department of Traumatology and Orthopedics, Inner Mongolia People’s Hospital, Hohhot, China
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The role of FOXD2-AS1 in cancer: a comprehensive study based on data mining and published articles. Biosci Rep 2021; 40:226886. [PMID: 33140822 PMCID: PMC7670568 DOI: 10.1042/bsr20190372] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 10/29/2020] [Accepted: 10/30/2020] [Indexed: 01/04/2023] Open
Abstract
Background and aims: Long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is aberrantly expressed in various cancers and associated with cancer progression. A comprehensive meta-analysis was performed based on published literature and data in the Gene Expression Omnibus database, and then the Cancer Genome Atlas (TCGA) dataset was used to assess the clinicopathological and prognostic value of FOXD2-AS1 in cancer patients. Methods: Gene Expression Omnibus databases of microarray data and published articles were used for meta-analysis, and TCGA dataset was also explored using the GEPIA analysis program. Hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the role of FOXD2-AS1 in cancers. Results: This meta-analysis included 21 studies with 2391 patients and 25 GEO datasets with 3311 patients. The pooled HRs suggested that highly expressed FOXD2-AS1 expression was correlated with poor overall survival (OS) and disease-free survival (DFS). Similar results were obtained by analysis of TCGA data for 9502 patients. The pooled results also indicated that FOXD2-AS1 expression was associated with bigger tumor size and advanced TNM stage, but was not related to age, gender, differentiation and lymph node metastasis. Conclusion: The present study demonstrated that FOXD2-AS1 is closely related to tumor size and TNM stage. Additionally, increased FOXD2-AS1 was a risk factor of OS and DFS in cancer patients, suggesting FOXD2-AS1 may be a potential biomarker in human cancers.
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Abstract
Osteoarthritis (OA) is considered the most frequent degenerative disease and is characterized by cartilage degradation and synovial inflammation. Fibroblast-like synoviocytes (FLSs) are vital to synovial inflammation in OA. Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and hyperinsulinemia (HINS) and has been demonstrated to be an independent risk factor for OA. Autophagy is involved in the processes of various inflammatory diseases, and autophagy inhibition can stimulate OA development. Thus, we aimed to investigate the role of insulin in the inflammatory phenotype and autophagy of FLSs in OA. The data showed that cell viability and proinflammatory cytokine production in FLSs were both increased after insulin stimulation. We also found that high insulin could promote macrophage infiltration and chemokine production but inhibited autophagy in FLSs. To further explore the potential mechanisms, the effects of insulin on PI3K/Akt/mTOR and NF-ĸB signaling activation were evaluated. The results indicated that insulin activated PI3K/Akt/mTOR/NF-ĸB signaling, and the above-mentioned inflammatory responses, including autophagy inhibition, were notably attenuated by specific signaling inhibitors in the presence of high insulin. Moreover, the data showed that a positive feedback loop existed between proinflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α) and PI3K/mTOR/Akt/NF-ĸB signaling in FLSs, and insulin enhanced this feedback loop to accelerate OA progression. Our study suggests that insulin may be a novel therapeutic strategy for OA prevention and treatment in the future.
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Affiliation(s)
- Li Qiao
- Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China
| | - Yi Li
- Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China
| | - Shui Sun
- Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
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Shao Q, Liu X, Su T, Ma C, Wang P. New Insights Into the Role of Seed Oil Body Proteins in Metabolism and Plant Development. FRONTIERS IN PLANT SCIENCE 2019; 10:1568. [PMID: 31921234 PMCID: PMC6914826 DOI: 10.3389/fpls.2019.01568] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 11/08/2019] [Indexed: 05/10/2023]
Abstract
Oil bodies (OBs) are ubiquitous dynamic organelles found in plant seeds. They have attracted increasing attention recently because of their important roles in plant physiology. First, the neutral lipids stored within these organelles serve as an initial, essential source of energy and carbon for seed germination and post-germinative growth of the seedlings. Secondly, they are involved in many other cellular processes such as stress responses, lipid metabolism, organ development, and hormone signaling. The biological functions of seed OBs are dependent on structural proteins, principally oleosins, caleosins, and steroleosins, which are embedded in the OB phospholipid monolayer. Oleosin and caleosin proteins are specific to plants and mainly act as OB structural proteins and are important for the biogenesis, stability, and dynamics of the organelle; whereas steroleosin proteins are also present in mammals and play an important role in steroid hormone metabolism and signaling. Significant progress using new genetic, biochemical, and imaging technologies has uncovered the roles of these proteins. Here, we review recent work on the structural or metabolic roles of these proteins in OB biogenesis, stabilization and degradation, lipid homeostasis and mobilization, hormone signal transduction, stress defenses, and various aspects of plant growth and development.
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Affiliation(s)
| | | | | | - Changle Ma
- Shandong Provincial Key Laboratory of Plant Stress, College of Life Sciences, Shandong Normal University, Jinan, China
| | - Pingping Wang
- Shandong Provincial Key Laboratory of Plant Stress, College of Life Sciences, Shandong Normal University, Jinan, China
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Nan H, Gao LZ. Genome-Wide Analysis of WRKY Genes and Their Response to Hormone and Mechanic Stresses in Carrot. Front Genet 2019; 10:363. [PMID: 31191596 PMCID: PMC6504813 DOI: 10.3389/fgene.2019.00363] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2018] [Accepted: 04/05/2019] [Indexed: 11/13/2022] Open
Abstract
The WRKY gene family plays a vital role in plant development and environment response. Although previous studies suggested that the WRKY genes in carrot (Kuroda type) involved in biotic and abiotic stress responses, the information of WRKY genes in the latest version of the carrot genome (Daucus carota v2.0, Nantes type carrot) and their response to hormone and injury stresses have not been reported. In this study, we performed a genome-wide analysis of WRKYs using a chromosome-scale genome assembly of carrot (Daucus carota subsp. sativus L.). We identified a total of 67 WRKY genes, which were further classified into the three groups. These WRKY genes are unevenly distributed on carrot chromosomes. We found that more than half of them were derived from whole-genome duplication (WGD) events, suggesting that WGDs have played a major role during the evolution of the WRKY gene family. We experimentally ascertained the expression divergence existed between WGD-derived WRKY duplicated gene pairs, which is indicative of functional differentiation between duplicated genes. Our analysis of cis-acting elements indicated that WRKY genes were transcriptionally regulated upon hormone and mechanic injury stresses. Gene expression analyses by qRT-PCR further presented that WRKY genes were involved in hormone and mechanic injury stresses.
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Affiliation(s)
- Hong Nan
- Plant Germplasm and Genomics Center, Germplasm Bank of Wild Species in Southwest China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Li-Zhi Gao
- Plant Germplasm and Genomics Center, Germplasm Bank of Wild Species in Southwest China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.,Institution of Genomics and Bioinformatics, South China Agricultural University, Guangzhou, China
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Elbers D, Scholten A, Koch KW. Zebrafish Recoverin Isoforms Display Differences in Calcium Switch Mechanisms. Front Mol Neurosci 2018; 11:355. [PMID: 30323742 PMCID: PMC6172410 DOI: 10.3389/fnmol.2018.00355] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 09/11/2018] [Indexed: 12/29/2022] Open
Abstract
Primary steps in vertebrate vision occur in rod and cone cells of the retina and require precise molecular switches in excitation, recovery, and adaptation. In particular, recovery of the photoresponse and light adaptation processes are under control of neuronal Ca2+ sensor (NCS) proteins. Among them, the Ca2+ sensor recoverin undergoes a pronounced Ca2+-dependent conformational change, a prototypical so-called Ca2+-myristoyl switch, which allows selective targeting of G protein-coupled receptor kinase. Zebrafish (Danio rerio) has gained attention as a model organism in vision research. It expresses four different recoverin isoforms (zRec1a, zRec1b, zRec2a, and zRec2b) that are orthologs to the one known mammalian variant. The expression pattern of the four isoforms cover both rod and cone cells, but the differential distribution in cones points to versatile functions of recoverin in these cell types. Initial functional studies on zebrafish larvae indicate different Ca2+-sensitive working modes for zebrafish recoverins, but experimental evidence is lacking so far. The aims of the present study are (1) to measure specific Ca2+-sensing properties of the different recoverin isoforms, (2) to ask whether switch mechanisms triggered by Ca2+ resemble that one observed with mammalian recoverin, and (3) to investigate a possible impact of an attached myristoyl moiety. For addressing these questions, we employ fluorescence spectroscopy, surface plasmon resonance (SPR), dynamic light scattering, and equilibrium centrifugation. Exposure of hydrophobic amino acids, due to the myristoyl switch, differed among isoforms and depended also on the myristoylation state of the particular recoverin. Ca2+-induced rearrangement of the protein-water shell was for all variants less pronounced than for the bovine ortholog indicating either a modified Ca2+-myristoyl switch or no switch. Our results have implications for a step-by-step response of recoverin isoforms to changing intracellular Ca2+ during illumination.
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Affiliation(s)
- Dana Elbers
- Department of Neuroscience, Biochemistry, University of Oldenburg, Oldenburg, Germany
| | - Alexander Scholten
- Department of Neuroscience, Biochemistry, University of Oldenburg, Oldenburg, Germany
| | - Karl-Wilhelm Koch
- Department of Neuroscience, Biochemistry, University of Oldenburg, Oldenburg, Germany
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Vasil'eva IN, Bespalov VG. [Plasma low-molecular-weight DNA in patients with chronic obstructive pulmonary disease]. TERAPEVT ARKH 2017; 89:24-28. [PMID: 28378725 DOI: 10.17116/terarkh201789324-28] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
AIM To determine plasma extracellular low-molecular-weight DNA (elmwDNA) as an indicator of apoptosis in patients with chronic obstructive pulmonary disease (COPD) in remission versus healthy donors, patients with chronic non-obstructive bronchitis (CNOB), and their first-degree relatives (FDRs). SUBJECTS AND METHODS The investigation recruited 110 participants, including 17 healthy donors, 31 patients with COPD, and 20 patients with CNOB in remission, 19 healthy FDRs of patients with COPD, and 23 healthy FDRs of those with SNOB. The plasma levels of elmwDNA were determined in the study participants. Nucleic acids were isolated by phenol/chloroform extraction, precipitated with ethanol, and treated with RNase; elmwDNA was analyzed by electrophoresis. RESULTS In patients with COPD, the mean level of elmwDNA was 7.8±2.0 ng/ml, which was 3.9 and 3.0 times statistically significantly lower than that in healthy donors and patients with SNOB, respectively; while the level of elmwDNA in the latter did not differ statistically significantly from that in healthy donors. In both the blood relatives of patients with COPD and FDRs of those with SNOB, the mean level of elmwDNA was not significantly different from that in healthy donors. The content of elmwDNA tended to increase in COPD patients aged 60-80 years as compared to those aged 45-59 years; that in both age groups was, however, significantly lower than in healthy donors of the same age. CONCLUSION The level of elmwDNA in plasma and, accordingly, apoptosis in the lung are reduced in patients with COPD in remission, whereas that is unchanged in those with SNOB. In patients with COPD, blood elmwDNA release is unrelated to heredity and varies little with age. The determination of elmwDNA is recommended for use in patients with COPD to assess apoptosis.
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Affiliation(s)
- I N Vasil'eva
- N.N. Petrov Research Institute of Oncology, Ministry of Health of Russia, Saint Petersburg, Russia; International Research Center 'Biotechnologies of the Third Millennium', University of Information Technologies, Mechanics, and Optics, Saint Petersburg, Russia
| | - V G Bespalov
- N.N. Petrov Research Institute of Oncology, Ministry of Health of Russia, Saint Petersburg, Russia; International Research Center 'Biotechnologies of the Third Millennium', University of Information Technologies, Mechanics, and Optics, Saint Petersburg, Russia
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Wang H, Wu Y, Yang X, Guo X, Cao X. SmLEA2, a gene for late embryogenesis abundant protein isolated from Salvia miltiorrhiza, confers tolerance to drought and salt stress in Escherichia coli and S. miltiorrhiza. PROTOPLASMA 2017; 254:685-696. [PMID: 27193100 DOI: 10.1007/s00709-016-0981-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/09/2016] [Accepted: 04/29/2016] [Indexed: 05/20/2023]
Abstract
Abiotic stresses, such as drought and high salinity, are major factors that limit plant growth and productivity. Late embryogenesis abundant (LEA) proteins are members of a diverse, multigene family closely associated with tolerance to abiotic stresses in numerous organisms. We examined the function of SmLEA2, previously isolated from Salvia miltiorrhiza, in defense responses to drought and high salinity. Phylogenetic analysis indicated that SmLEA2 belongs to the LEA_2 subfamily. Its overexpression in Escherichia coli improved growth performance when compared with the control under salt and drought stresses. We further characterized its roles in S. miltiorrhiza through overexpression and RNAi-mediated silencing. In response to drought and salinity treatments, transgenic plants overexpressing SmLEA2 exhibited significantly increased superoxide dismutase activity, reduced levels of lipid peroxidation, and more vigorous growth than empty-vector control plants did. However, transgenic lines in which expression was suppressed showed the opposite results. Our data demonstrate that SmLEA2 plays an important role in the abiotic stress response and its overexpression in transgenic S. miltiorrhiza improves tolerance to excess salt and drought conditions.
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Affiliation(s)
- Huaiqin Wang
- Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University, Xi'an, 710062, China
| | - Yucui Wu
- Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University, Xi'an, 710062, China
| | - Xinbing Yang
- Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University, Xi'an, 710062, China
| | - Xiaorong Guo
- Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University, Xi'an, 710062, China
| | - Xiaoyan Cao
- Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest of China, Shaanxi Normal University, Xi'an, 710062, China.
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Funke S, Perumal N, Beck S, Gabel-Scheurich S, Schmelter C, Teister J, Gerbig C, Gramlich OW, Pfeiffer N, Grus FH. Glaucoma related Proteomic Alterations in Human Retina Samples. Sci Rep 2016; 6:29759. [PMID: 27425789 PMCID: PMC4947915 DOI: 10.1038/srep29759] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 06/24/2016] [Indexed: 01/23/2023] Open
Abstract
Glaucoma related proteomic changes have been documented in cell and animal models. However, proteomic studies investigating on human retina samples are still rare. In the present work, retina samples of glaucoma and non-glaucoma control donors have been examined by a state-of-the-art mass spectrometry (MS) workflow to uncover glaucoma related proteomic changes. More than 600 proteins could be identified with high confidence (FDR < 1%) in human retina samples. Distinct proteomic changes have been observed in 10% of proteins encircling mitochondrial and nucleus species. Numerous proteins showed a significant glaucoma related level change (p < 0.05) or distinct tendency of alteration (p < 0.1). Candidates were documented to be involved in cellular development, stress and cell death. Increase of stress related proteins and decrease of new glaucoma related candidates, ADP/ATP translocase 3 (ANT3), PC4 and SRFS1-interacting protein 1 (DFS70) and methyl-CpG-binding protein 2 (MeCp2) could be documented by MS. Moreover, candidates could be validated by Accurate Inclusion Mass Screening (AIMS) and immunostaining and supported for the retinal ganglion cell layer (GCL) by laser capture microdissection (LCM) in porcine and human eye cryosections. The workflow allowed a detailed view into the human retina proteome highlighting new molecular players ANT3, DFS70 and MeCp2 associated to glaucoma.
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Affiliation(s)
- Sebastian Funke
- Experimental Ophthalmology, Department of Ophthalmology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Natarajan Perumal
- Experimental Ophthalmology, Department of Ophthalmology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Sabine Beck
- Experimental Ophthalmology, Department of Ophthalmology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Silke Gabel-Scheurich
- Experimental Ophthalmology, Department of Ophthalmology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Carsten Schmelter
- Experimental Ophthalmology, Department of Ophthalmology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Julia Teister
- Experimental Ophthalmology, Department of Ophthalmology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Claudia Gerbig
- Experimental Ophthalmology, Department of Ophthalmology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Oliver W Gramlich
- Experimental Ophthalmology, Department of Ophthalmology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.,Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa, USA
| | - Norbert Pfeiffer
- Experimental Ophthalmology, Department of Ophthalmology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
| | - Franz H Grus
- Experimental Ophthalmology, Department of Ophthalmology, University Medical Center, Johannes Gutenberg University, Mainz, Germany
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Chronic iron deficiency as an emerging risk factor for osteoporosis: a hypothesis. Nutrients 2015; 7:2324-44. [PMID: 25849944 PMCID: PMC4425147 DOI: 10.3390/nu7042324] [Citation(s) in RCA: 115] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Revised: 03/18/2015] [Accepted: 03/19/2015] [Indexed: 01/25/2023] Open
Abstract
Iron is essential in oxygen transport and participates in many enzymatic systems in the body, with important roles in collagen synthesis and vitamin D metabolism. The relationship between iron and bone health comes from clinical observations in iron overload patients who suffered bone loss. The opposite scenario—whether iron deficiency, with or without anemia, affects bone metabolism—has not been fully addressed. This is of great interest, as this nutrient deficiency is a worldwide public health problem and at the same time osteoporosis and bone alterations are highly prevalent. This review presents current knowledge on nutritional iron deficiency and bone remodeling, the biomarkers to evaluate iron status and bone formation and resorption, and the link between iron and bone metabolism. Finally, it is hypothesized that chronic iron deficiency induces bone resorption and risk of osteoporosis, thus complete recovery from anemia and its prevention should be promoted in order to improve quality of life including bone health. Several mechanisms are suggested; hence, further investigation on the possible impact of chronic iron deficiency on the development of osteoporosis is needed.
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Baghaban Eslaminejad M, Malakooty Poor E. Mesenchymal stem cells as a potent cell source for articular cartilage regeneration. World J Stem Cells 2014; 6:344-354. [PMID: 25126383 PMCID: PMC4131275 DOI: 10.4252/wjsc.v6.i3.344] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Revised: 12/07/2013] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
Since articular cartilage possesses only a weak capacity for repair, its regeneration potential is considered one of the most important challenges for orthopedic surgeons. The treatment options, such as marrow stimulation techniques, fail to induce a repair tissue with the same functional and mechanical properties of native hyaline cartilage. Osteochondral transplantation is considered an effective treatment option but is associated with some disadvantages, including donor-site morbidity, tissue supply limitation, unsuitable mechanical properties and thickness of the obtained tissue. Although autologous chondrocyte implantation results in reasonable repair, it requires a two-step surgical procedure. Moreover, chondrocytes expanded in culture gradually undergo dedifferentiation, so lose morphological features and specialized functions. In the search for alternative cells, scientists have found mesenchymal stem cells (MSCs) to be an appropriate cellular material for articular cartilage repair. These cells were originally isolated from bone marrow samples and further investigations have revealed the presence of the cells in many other tissues. Furthermore, chondrogenic differentiation is an inherent property of MSCs noticed at the time of the cell discovery. MSCs are known to exhibit homing potential to the damaged site at which they differentiate into the tissue cells or secrete a wide spectrum of bioactive factors with regenerative properties. Moreover, these cells possess a considerable immunomodulatory potential that make them the general donor for therapeutic applications. All of these topics will be discussed in this review.
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Yu SS, Zhu X. Role of NADPH oxidase family members in promoting liver fibrosis. Shijie Huaren Xiaohua Zazhi 2014; 22:2710-2715. [DOI: 10.11569/wcjd.v22.i19.2710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Liver fibrosis is one of hepatic wound-repair responses to a variety of chronic liver injuries, which is characterized by excessive deposition of extracellular matrix. Increasing evidence indicates that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and oxidative stress caused by reactive oxygen species play a key role in liver fibrosis. NADPH oxidase is a multi-subunit complex. In the liver, both phagocytic and non-phagocytic NADPH oxidases are functionally expressed. They have a significant fibrogenic effect on the hepatic stellate cells, the main cell type causing liver fibrosis. In this paper, we review the recent advances in understanding the role of the NADPH oxidase family in the occurrence and development of liver fibrosis.
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Peng Z, Wang CX, Fang EH, Wang GB, Tong Q. Role of epithelial-mesenchymal transition in gastric cancer initiation and progression. World J Gastroenterol 2014; 20:5403-5410. [PMID: 24833870 PMCID: PMC4017055 DOI: 10.3748/wjg.v20.i18.5403] [Citation(s) in RCA: 164] [Impact Index Per Article: 14.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2013] [Revised: 01/09/2014] [Accepted: 01/20/2014] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer is one of the most common malignant tumors worldwide. Due to its intricate initiation and progression mechanisms, early detection and effective treatment of gastric cancer are difficult to achieve. The epithelial-mesenchymal transition (EMT) is characterized as a fundamental process that is critical for embryonic development, wound healing and fibrotic disease. Recent evidence has established that aberrant EMT activation in the human stomach is closely associated with gastric carcinogenesis and tumor progression. EMT activation endows gastric epithelial cells with increased characteristics of mesenchymal cells and reduces their epithelial features. Moreover, mesenchymal cells tend to dedifferentiate and acquire stem cell or tumorigenic phenotypes such as invasion, metastasis and apoptosis resistance as well as drug resistance during EMT progression. There are a number of molecules that indicate the stage of EMT (e.g., E-cadherin, an epithelial cell biomarker); therefore, certain transcriptional proteins, especially E-cadherin transcriptional repressors, may participate in the regulation of EMT. In addition, EMT regulation may be associated with certain epigenetic mechanisms. The aforementioned molecules can be used as early diagnostic markers for gastric cancer, and EMT regulation can provide potential targets for gastric cancer therapy. Here, we review the role of these aspects of EMT in gastric cancer initiation and development.
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