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1
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Lighting up trace carbon monoxide and residual palladium species by a low cytotoxic mitochondria targetable red fluorescent probe: Its large scaled applications. Talanta 2023; 258:124454. [PMID: 36924639 DOI: 10.1016/j.talanta.2023.124454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Revised: 03/06/2023] [Accepted: 03/11/2023] [Indexed: 03/14/2023]
Abstract
High levels of residual palladium can lead to serious negative health effects. Carbon monoxide (CO) is a significant gasotransmitter in transporting intermolecular and intramolecular signals to balance several physiological processes. Therefore, there is a need for rapid detection of CO and palladium residue. To address these issues, we have designed a novel light-up fluorescent probe for the detection of Pd and CO. It can not only detect Pd and CO selectively with a remarkable chromogenic and red fluorescent response over other metal ions allowing detection with naked eyes but also discriminate Pd0 and Pd2+/Pd4+ species. The detection reaction is confirmed by HPLC analysis. The probe demonstrates biocompatibility and mitochondrial target ability for potential biological applications. The practical applications based on drug residue and soil analysis, and smartphone have been successfully performed. Bioimaging of the concentration change of Pd and CO in HeLa cells using the probe is successfully applied. Therefore, the present approach can provide early diagnosis of Pd and CO with low detection limit, low cytotoxicity, high selectivity, and sensitivity.
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2
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Ye M, Tan Q, Jiang D, Li J, Yao C, Zhou Y. Deep-Depth Imaging of Hepatic Ischemia/Reperfusion Injury Using a Carbon Monoxide-Activated Upconversion Luminescence Nanosystem. ACS APPLIED MATERIALS & INTERFACES 2022; 14:52659-52669. [PMID: 36377946 DOI: 10.1021/acsami.2c15960] [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: 06/16/2023]
Abstract
Exploring a chemical imaging tool for visualizing the endogenous CO biosignaling molecule is of great importance in understanding the pathophysiological functions of CO in complex biological systems. Most of the existing CO fluorescent probes show excitation and emission in the region of ultraviolet and visible light, which are not suitable for application in in vivo deep-depth imaging of CO. Herein, a new near-infrared (NIR) to NIR upconversion luminescence (UCL) nanosystem for in vivo visualization of CO was developed, which possesses the merits of high selectivity and sensitivity, a deep tissue penetration depth, and a high signal-to-noise ratio. In this design, upon interaction with CO, the maxima absorption peak of the nanosystem showed a significant blue shift from 795 nm to 621 nm and triggered a remarkable turn-on NIR UCL signal due to the luminescence resonance energy transfer process. Leveraging this nanosystem, we achieved an NIR UCL visualization of the generation of CO biosignals caused by hypoxic, acute inflammation, or ischemic injury in living cells, zebrafish, and mice. Moreover, the protective effect of CO in zebrafish models of oxygen and glucose deprivation/reperfusion (OGD/R) and mice models of lipopolysaccharide-induced oxidative stress (LOS) and hepatic ischemia/reperfusion (HI/R) was also further verified. Therefore, this work discloses that the nanosystem not only serves as a promising nanoplatform to study biological signaling pathways of CO in pathophysiological events, but may also provide a powerful tool for HI/R injury diagnosis.
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Affiliation(s)
- Minan Ye
- College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, P. R. China
| | - Qi Tan
- College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, P. R. China
| | - Detao Jiang
- College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, P. R. China
| | - Jingyun Li
- Nanjing Maternal and Child Health Medical Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, 123rd Tianfei Street, Mochou Road, Nanjing 210004, China
| | - Cheng Yao
- College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, P. R. China
| | - Yi Zhou
- College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, P. R. China
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3
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Ye M, Zhang J, Jiang D, Tan Q, Li J, Yao C, Zhu C, Zhou Y. A Hemicyanine-Assembled Upconversion Nanosystem for NIR-Excited Visualization of Carbon Monoxide Bio-Signaling In Vivo. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2022; 18:e2202263. [PMID: 35713262 DOI: 10.1002/smll.202202263] [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] [Received: 04/11/2022] [Revised: 05/17/2022] [Indexed: 06/15/2023]
Abstract
Carbon monoxide (CO) is considered as the second gasotransmitter involved in a series of physiological and pathological processes. Although a number of organic fluorescent probes have been developed for imaging CO, these probes display excitation within the ultraviolet or visible range, which restrict their applications in the complex biosystems. In the present work, a strategy is developed to construct an upconversion nanoparticles-based nanosystem for upconversion luminescent (UCL) sensing CO. This nanosystem exhibits a fast response to CO with high sensitivity and selectivity in aqueous solution by a near-infrared-excited ratiometric UCL detection method. Meanwhile, laser scanning upconversion luminescence microscope experiments demonstrate that this nanosystem can visualize the endogenous CO bio-signaling in living cells, deep tissues, zebrafish, and living mice by ratiometric UCL imaging. In particular, this nanosystem has been successfully employed in visualization of the endogenous CO bio-signaling through up-regulation of heme oxygenase-1 (HO-1) in the progression of hypoxia, acute inflammation, or ischemic injury. This work demonstrates that the outstanding performance of the nanosystem not only can provide an effective tool for further understanding the role of CO in the physiological and pathological environment, but also may have great potential ability for tracking the expression of HO-1 in living systems.
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Affiliation(s)
- Minan Ye
- College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, 211816, P. R. China
| | - Jie Zhang
- College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, 211816, P. R. China
| | - Detao Jiang
- College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, 211816, P. R. China
| | - Qi Tan
- College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, 211816, P. R. China
| | - Jingyun Li
- Department of Plastic & Cosmetic Surgery, Maternal and Child Health Medical Institute, Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, P. R. China
| | - Cheng Yao
- College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, 211816, P. R. China
| | - Chenjie Zhu
- College of Biotechnology and Pharmaceutical Engineering, The Synergetic Innovation Center for Advanced Materials, Nanjing Tech University, No. 30, South Puzhu Road, Nanjing, 211816, P. R. China
| | - Yi Zhou
- College of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing, 211816, P. R. China
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Wang Y, Wu J, Wang D, Yang R, Liu Q. Traditional Chinese Medicine Targeting Heat Shock Proteins as Therapeutic Strategy for Heart Failure. Front Pharmacol 2022; 12:814243. [PMID: 35115946 PMCID: PMC8804377 DOI: 10.3389/fphar.2021.814243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Accepted: 12/21/2021] [Indexed: 11/13/2022] Open
Abstract
Heart failure (HF) is the terminal stage of multifarious heart diseases and is responsible for high hospitalization rates and mortality. Pathophysiological mechanisms of HF include cardiac hypertrophy, remodeling and fibrosis resulting from cell death, inflammation and oxidative stress. Heat shock proteins (HSPs) can ameliorate folding of proteins, maintain protein structure and stability upon stress, protect the heart from cardiac dysfunction and ameliorate apoptosis. Traditional Chinese medicine (TCM) regulates expression of HSPs and has beneficial therapeutic effect in HF. In this review, we summarized the function of HSPs in HF and the role of TCM in regulating expression of HSPs. Studying the regulation of HSPs by TCM will provide novel ideas for the study of the mechanism and treatment of HF.
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Affiliation(s)
- Yanchun Wang
- Shenyang the Tenth People’s Hospital, Shenyang, China
| | - Junxuan Wu
- Shunde Hospital of Guangzhou University of Chinese Medicine, Foshan, China
| | - Dawei Wang
- Shunde Hospital of Guangzhou University of Chinese Medicine, Foshan, China
- *Correspondence: Qing Liu, ; Dawei Wang, ; Rongyuan Yang,
| | - Rongyuan Yang
- The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine-Zhuhai Hospital, Zhuhai, China
- *Correspondence: Qing Liu, ; Dawei Wang, ; Rongyuan Yang,
| | - Qing Liu
- The Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine-Zhuhai Hospital, Zhuhai, China
- *Correspondence: Qing Liu, ; Dawei Wang, ; Rongyuan Yang,
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5
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Liu H, Nguyen HH, Yoon KT, Lee SS. Pathogenic Mechanisms Underlying Cirrhotic Cardiomyopathy. FRONTIERS IN NETWORK PHYSIOLOGY 2022; 2:849253. [PMID: 36926084 PMCID: PMC10013066 DOI: 10.3389/fnetp.2022.849253] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 02/18/2022] [Indexed: 12/14/2022]
Abstract
Cardiac dysfunction associated with cirrhosis in the absence of preexisting heart disease is a condition known as cirrhotic cardiomyopathy (CCM). Cardiac abnormalities consist of enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM may contribute to cardiovascular morbidity and mortality after liver transplantation and other major surgeries, and also to the pathogenesis of hepatorenal syndrome. The underlying mechanisms of CCM are poorly understood and as such medical therapy is an area of unmet medical need. The present review focuses on the pathogenic mechanisms responsible for development of CCM. The two major concurrent mechanistic pathways are the inflammatory phenotype due to portal hypertension, and protein/lipid synthetic/metabolic defects due to cirrhosis and liver insufficiency. The inflammatory phenotype arises from intestinal congestion due to portal hypertension, resulting in bacteria/endotoxin translocation into the systemic circulation. The cytokine storm associated with inflammation, particularly TNFα acting via NFκB depresses cardiac function. They also stimulate two evanescent gases, nitric oxide and carbon monoxide which produce cardiodepression by cGMP. Inflammation also stimulates the endocannabinoid CB-1 pathway. These systems inhibit the stimulatory beta-adrenergic contractile pathway. The liver insufficiency of cirrhosis is associated with defective synthesis or metabolism of several substances including proteins and lipids/lipoproteins. The protein defects including titin and collagen contribute to diastolic dysfunction. Other protein abnormalities such as a switch of myosin heavy chain isoforms result in systolic dysfunction. Lipid biochemical changes at the cardiac sarcolemmal plasma membrane result in increased cholesterol:phospholipid ratio and decreased membrane fluidity. Final common pathway changes involve abnormal cardiomyocyte intracellular ion kinetics, particularly calcium. In conclusion, cirrhotic cardiomyopathy is caused by two pathways of cellular and molecular dysfunction/damage due to hepatic insufficiency and portal hypertension.
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Affiliation(s)
- Hongqun Liu
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB, Canada
| | - Henry H Nguyen
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB, Canada
| | - Ki Tae Yoon
- Liver Center, Pusan National University Yangsan Hospital, Yangsan, South Korea
| | - Samuel S Lee
- Liver Unit, University of Calgary Cumming School of Medicine, Calgary, AB, Canada
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Tian Y, Jiang WL, Wang WX, Peng J, Li XM, Li Y, Li CY. The construction of a near-infrared fluorescent probe with dual advantages for imaging carbon monoxide in cells and in vivo. Analyst 2021; 146:118-123. [PMID: 33089835 DOI: 10.1039/d0an01719a] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
As a kind of toxic gas, carbon monoxide (CO) can hinder uptake of oxygen in humans. However, more and more studies have shown that CO is an important gaseous messenger in the body and playing an indispensable role in intracellular signaling pathways. So, it is necessary to develop an analytical method to study CO in living organisms. Although there are many CO-responsive probes, most of them have the disadvantages of a small Stokes shift or short emission wavelength. In order to address the above issue, a novel probe (FDX-CO) with a large Stokes shift (190 nm) and long emission wavelength (770 nm) was firstly synthesized to detect CO. The probe shows high sensitivity and superior selectivity toward CO. Moreover, the probe was successfully used for visualizing exogenous and endogenous CO in cells by fluorescence imaging, 3D quantification analysis and flow cytometric analysis. More importantly, FDX-CO could excellently detect CO in mice, which suggests that this probe has the potential ability to image CO in vivo. This probe can be viewed as a useful tool in the research of CO.
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Affiliation(s)
- Yang Tian
- Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, 411105, PR China.
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Du F, Qu Y, Li M, Tan X. Mitochondria-targetable ratiometric fluorescence probe for carbon monoxide based on naphthalimide derivatives. Anal Bioanal Chem 2021; 413:1395-1403. [PMID: 33404745 DOI: 10.1007/s00216-020-03103-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Revised: 11/25/2020] [Accepted: 11/27/2020] [Indexed: 01/28/2023]
Abstract
The design of ratiometric probes for imaging of carbon monoxide (CO) in subcellular organelles is critical to elucidate its biological and pathological functions. In this work, we establish a ratiometric fluorescent probe (Mito-NIB-CO) for imaging of CO in mitochondria. The mitochondria-targeting unit (triphenylphosphonium moiety) and CO-responsive unit (allyl ether moiety) are covalently linking into the single molecule (Mito-NIB-CO) to achieve the multifunctional effect. Upon being treated with CO, Mito-NIB-CO underwent the cleavage of allyl ether element in the presence of PdCl2, resulting in the structural and spectral conversion. This characteristic afforded Mito-NIB-CO to be a ratiometric probe for CO with two fluorescent emission bands. Additionally, the probe Mito-NIB-CO exhibited other distinct merits, including preeminent selectivity and sensitivity. What's more, profiting from triphenylphosphonium moiety, the probe Mito-NIB-CO can specifically target the mitochondria and realize quantitative detection of exogenous/endogenous CO in mitochondria. Graphical abstract.
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Affiliation(s)
- Fangkai Du
- Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Key Laboratory of Guangxi Colleges and Universities for Food Safety and Pharmaceutical Analytical Chemistry, School of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Nanning, 530008, People's Republic of China.
| | - Yunting Qu
- Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Key Laboratory of Guangxi Colleges and Universities for Food Safety and Pharmaceutical Analytical Chemistry, School of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Nanning, 530008, People's Republic of China
| | - Mengru Li
- Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Key Laboratory of Guangxi Colleges and Universities for Food Safety and Pharmaceutical Analytical Chemistry, School of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Nanning, 530008, People's Republic of China
| | - Xuecai Tan
- Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Key Laboratory of Guangxi Colleges and Universities for Food Safety and Pharmaceutical Analytical Chemistry, School of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Nanning, 530008, People's Republic of China.
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8
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A near-infrared fluorescent probe for imaging endogenous carbon monoxide in living systems with a large Stokes shift. Talanta 2019; 201:40-45. [PMID: 31122441 DOI: 10.1016/j.talanta.2019.03.111] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2019] [Revised: 03/23/2019] [Accepted: 03/30/2019] [Indexed: 01/27/2023]
Abstract
Near-infrared (NIR) fluorescent probes with a large Stokes shift are very practical tools for bioimaging applications. Carbon monoxide (CO) is a key gaseous signal molecule and its imaging in living systems has attracted great attention in recent years. In this work, a very easy-to-get NIR fluorescent probe with a remarkable large pseudo-Stokes shift (238 nm) for detection of CO was reported. This probe was found to show a rapid NIR fluorescent turn-on response for CO with high selectivity, high sensitivity and a low detection limit (38 nM). Moreover, imaging CO in living cells and animals with this probe was successfully applied with a high signal-to-noise ratio. The results indicate that this probe can be used as a new practical tool for imaging of endogenous CO in living systems.
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9
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Santos-Junior VDA, Lollo PCB, Cantero MA, Moura CS, Amaya-Farfan J, Morato PN. Heat Shock Proteins: Protection and Potential Biomarkers for Ischemic Injury of Cardiomyocytes After Surgery. Braz J Cardiovasc Surg 2019; 33:291-302. [PMID: 30043923 PMCID: PMC6089130 DOI: 10.21470/1678-9741-2017-0169] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Accepted: 02/05/2018] [Indexed: 11/24/2022] Open
Abstract
The heat shock proteins are endogenous proteins with the ability to act as
molecular chaperones. Methods that provide cell protection by way of some damage
can positively influence the results of surgery. The present review summarizes
current knowledge concerning the cardioprotective role of the heat shock
proteins as occurs in heart damage, including relevant information about the
stresses that regulate the expression of these proteins and their potential role
as biomarkers of heart disease.
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Affiliation(s)
| | | | - Marcos Antonio Cantero
- Faculdade de Ciências da Saúde (FCS) da Universidade Federal da Grande Dourados (UFGD), Dourados, MS, Brazil
| | - Carolina Soares Moura
- Faculdade de Engenharia de Alimentos (FEA) da Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil
| | - Jaime Amaya-Farfan
- Faculdade de Engenharia de Alimentos (FEA) da Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil
| | - Priscila Neder Morato
- Faculdade de Engenharia de Alimentos (FEA) da Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil
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10
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Li SJ, Zhou DY, Li YF, Yang B, Ou-Yang J, Jie J, Liu J, Li CY. Mitochondria-targeted near-infrared fluorescent probe for the detection of carbon monoxide in vivo. Talanta 2018; 188:691-700. [PMID: 30029433 DOI: 10.1016/j.talanta.2018.06.046] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2018] [Revised: 06/08/2018] [Accepted: 06/13/2018] [Indexed: 12/25/2022]
Abstract
Carbon monoxide is a critical gasotransmitter in the body and related with mitochondrial respiration. To date, various fluorescent probes for CO have been well proposed, but two main problems remain. One is that most of the probes are not mitochondria-targeting, even if the probes claim to be able to detect CO in living cells. The other is that the probes for CO display excitation and emission within the ultraviolet or visible range, which hinders their applications in vivo. Herein, a hemicyanine-based near-infrared (NIR) fluorescent probe named CyAPC is first synthesized and used to detect mitochondrial CO. The characteristics of probe CyAPC are as follows: (1) The fluorescence emission of the sensing system is at 736 nm belonging to NIR region, which is suitable for bioimaging in vivo. (2) CyAPC, a positively charged molecule, would have a high tendency to localize in mitochondria of cells. (3) The fluorescence change of the probe is attributed to the fact that CO with Pd2+ induced cleavage of the allyl formate group from the probe and CyAPC (fluorescence off) is transformed into CyOH (fluorescence on), which is proved by HPLC, MS and DFT calculation. (4) The NIR fluorescent probe is applied for the detection of exogenous and endogenous CO in various biological samples such as cell, tissue and in vivo with satisfactory results.
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Affiliation(s)
- Song-Jiao Li
- Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China
| | - Dong-Ye Zhou
- Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China
| | - Yong-Fei Li
- Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China; College of Chemical Engineering, Xiangtan University, Xiangtan 411105, PR China
| | - Bin Yang
- Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China
| | - Juan Ou-Yang
- Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China
| | - Jia Jie
- College of Chemical Engineering, Xiangtan University, Xiangtan 411105, PR China.
| | - Juan Liu
- Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China
| | - Chun-Yan Li
- Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan 411105, PR China; State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry & Chemical Engineering, Hunan University, Changsha 410082, PR China.
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Tian X, Liu X, Wang A, Lau C, Lu J. Bioluminescence Imaging of Carbon Monoxide in Living Cells and Nude Mice Based on Pd0-Mediated Tsuji–Trost Reaction. Anal Chem 2018; 90:5951-5958. [DOI: 10.1021/acs.analchem.8b01102] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Affiliation(s)
- Xiaodong Tian
- School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China
| | - Xinda Liu
- School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China
| | - Anni Wang
- School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China
| | - Choiwan Lau
- School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China
| | - Jianzhong Lu
- School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China
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12
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Li Y, Wang X, Yang J, Xie X, Li M, Niu J, Tong L, Tang B. Fluorescent Probe Based on Azobenzene-Cyclopalladium for the Selective Imaging of Endogenous Carbon Monoxide under Hypoxia Conditions. Anal Chem 2016; 88:11154-11159. [PMID: 27748113 DOI: 10.1021/acs.analchem.6b03376] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Carbon monoxide (CO), a crucial gas message molecule, plays an important role in the regulation of physiological and pathological process. Hypoxia-induced CO is involved in modulating various cellular activities, including signal transduction, proliferation, and apoptosis. However, tracking CO fluctuation in the hypoxic cells is still a challenge due to lack of straightforward, visualized, and noninvasive tools. In this work, based on metal palladium-catalyzed reaction, we present the rational design, synthesis, and biological utility of an azobenzene-cyclopalladium-based fluorescent probe, ACP-2, for CO monitoring. ACP-2 exhibits capacity of detecting CO in aqueous buffer solution and live cells with high sensitivity and specificity. Utilizing ACP-2, we displayed a direct and visual evidence of endogenous CO up-regulation in live cells induced by hypoxia. Moreover, CO up-regulation during oxygen-glucose deprivation/reperfusion (OGD/R) was also imaged and certified by ACP-2.
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Affiliation(s)
- Yong Li
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University , Jinan 250014, P. R. China
| | - Xu Wang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University , Jinan 250014, P. R. China
| | - Jie Yang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University , Jinan 250014, P. R. China
| | - Xilei Xie
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University , Jinan 250014, P. R. China
| | - Mengmeng Li
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University , Jinan 250014, P. R. China
| | - Jinye Niu
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University , Jinan 250014, P. R. China
| | - Lili Tong
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University , Jinan 250014, P. R. China
| | - Bo Tang
- College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University , Jinan 250014, P. R. China
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13
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Gassanov N, Caglayan E, Semmo N, Massenkeil G, Er F. Cirrhotic cardiomyopathy: A cardiologist’s perspective. World J Gastroenterol 2014; 20:15492-15498. [PMID: 25400434 PMCID: PMC4229515 DOI: 10.3748/wjg.v20.i42.15492] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2013] [Revised: 04/01/2014] [Accepted: 06/13/2014] [Indexed: 02/06/2023] Open
Abstract
Cardiac dysfunction is frequently observed in patients with cirrhosis, and has long been linked to the direct toxic effect of alcohol. Cirrhotic cardiomyopathy (CCM) has recently been identified as an entity regardless of the cirrhosis etiology. Increased cardiac output due to hyperdynamic circulation is a pathophysiological hallmark of the disease. The underlying mechanisms involved in pathogenesis of CCM are complex and involve various neurohumoral and cellular pathways, including the impaired β-receptor and calcium signaling, altered cardiomyocyte membrane physiology, elevated sympathetic nervous tone and increased activity of vasodilatory pathways predominantly through the actions of nitric oxide, carbon monoxide and endocannabinoids. The main clinical features of CCM include attenuated systolic contractility in response to physiologic or pharmacologic strain, diastolic dysfunction, electrical conductance abnormalities and chronotropic incompetence. Particularly the diastolic dysfunction with impaired ventricular relaxation and ventricular filling is a prominent feature of CCM. The underlying mechanism of diastolic dysfunction in cirrhosis is likely due to the increased myocardial wall stiffness caused by myocardial hypertrophy, fibrosis and subendothelial edema, subsequently resulting in high filling pressures of the left ventricle and atrium. Currently, no specific treatment exists for CCM. The liver transplantation is the only established effective therapy for patients with end-stage liver disease and associated cardiac failure. Liver transplantation has been shown to reverse systolic and diastolic dysfunction and the prolonged QT interval after transplantation. Here, we review the pathophysiological basis and clinical features of cirrhotic cardiomyopathy, and discuss currently available limited therapeutic options.
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The role of Nrf2-mediated pathway in cardiac remodeling and heart failure. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2014; 2014:260429. [PMID: 25101151 PMCID: PMC4102082 DOI: 10.1155/2014/260429] [Citation(s) in RCA: 129] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/26/2014] [Revised: 04/12/2014] [Accepted: 04/30/2014] [Indexed: 12/30/2022]
Abstract
Heart failure (HF) is frequently the consequence of sustained, abnormal neurohormonal, and mechanical stress and remains a leading cause of death worldwide. The key pathophysiological process leading to HF is cardiac remodeling, a term referring to maladaptation to cardiac stress at the molecular, cellular, tissue, and organ levels. HF and many of the conditions that predispose one to HF are associated with oxidative stress. Increased generation of reactive oxygen species (ROS) in the heart can directly lead to increased necrosis and apoptosis of cardiomyocytes which subsequently induce cardiac remodeling and dysfunction. Nuclear factor-erythroid-2- (NF-E2-) related factor 2 (Nrf2) is a transcription factor that controls the basal and inducible expression of a battery of antioxidant genes and other cytoprotective phase II detoxifying enzymes that are ubiquitously expressed in the cardiovascular system. Emerging evidence has revealed that Nrf2 and its target genes are critical regulators of cardiovascular homeostasis via the suppression of oxidative stress, which is the key player in the development and progression of HF. The purpose of this review is to summarize evidence that activation of Nrf2 enhances endogenous antioxidant defenses and counteracts oxidative stress-associated cardiac remodeling and HF.
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Haines DD, Lekli I, Teissier P, Bak I, Tosaki A. Role of haeme oxygenase-1 in resolution of oxidative stress-related pathologies: focus on cardiovascular, lung, neurological and kidney disorders. Acta Physiol (Oxf) 2012; 204:487-501. [PMID: 22118298 DOI: 10.1111/j.1748-1716.2011.02387.x] [Citation(s) in RCA: 90] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The present review examines the role of the cytoprotective enzyme haeme oxygenase-1 (HO-1) in adaptive responses to inflammatory disease and explores strategies for its clinical use, with particular emphasis on use of therapeutic use of the enzyme using phytochemical inducers of HO-1 such as extracts of Ginkgo biloba, curcumin, and flavonoids extracted from seeds of the sour cherry (Prunus cerasus). This laboratory has identified strategies by which combinations of dietary phytochemicals may be configured to synergistically strengthen immunoregulatory mechanisms that normally prevent inflammation from leading to disease. A major focus of this research initiative has been HO-1, which is capable of substantially reducing oxidative stress by several mechanisms. HO-1 metabolizes haeme that accumulates in tissues because of red blood cell turnover. Two products of this degradation - carbon monoxide (CO) and bilirubin - have potent capacity for reducing oxidative stress and for counteracting its effects. A description will be provided of how HO-1 products maintain healthy tissue function and remediate oxidative tissue damage. This will be explored in four major organ systems, including the cardiovascular system, the lungs, the central nervous system and the kidneys. Particular focus will be given to the physiological coordination of cardiovascular functions mediated by CO produced by HO-1 and to nitric oxide (NO), a gaseous second messenger expressed by nitric oxide synthetase. A major unifying theme of the present review is an exploration of the potential use of dietary phytochemical formulations as tools for the clinical application of HO-1 in therapeutic reduction of oxidative stressors, with resultant improved treatment of inflammatory pathologies.
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Affiliation(s)
- D D Haines
- Department of Pharmacology, Faculty of Pharmacy, Health and Science Center, University of Debrecen, Hungary
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16
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Wang G, Hamid T, Keith RJ, Zhou G, Partridge CR, Xiang X, Kingery JR, Lewis RK, Li Q, Rokosh DG, Ford R, Spinale FG, Riggs DW, Srivastava S, Bhatnagar A, Bolli R, Prabhu SD. Cardioprotective and antiapoptotic effects of heme oxygenase-1 in the failing heart. Circulation 2010; 121:1912-25. [PMID: 20404253 DOI: 10.1161/circulationaha.109.905471] [Citation(s) in RCA: 202] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Heme oxygenase-1 (HO-1) is an inducible stress-response protein that imparts antioxidant and antiapoptotic effects. However, its pathophysiological role in cardiac remodeling and chronic heart failure (HF) is unknown. We hypothesized that induction of HO-1 in HF alleviates pathological remodeling. METHODS AND RESULTS Adult male nontransgenic and myocyte-restricted HO-1 transgenic mice underwent either sham operation or coronary ligation to induce HF. Four weeks after ligation, nontransgenic HF mice exhibited postinfarction left ventricular (LV) remodeling and dysfunction, hypertrophy, fibrosis, oxidative stress, apoptosis, and reduced capillary density, associated with a 2-fold increase in HO-1 expression in noninfarcted myocardium. Compared with nontransgenic mice, HO-1 transgenic HF mice exhibited significantly (P<0.05) improved postinfarction survival (94% versus 57%) and less LV dilatation (end-diastolic volume, 46+/-8 versus 85+/-32 microL), mechanical dysfunction (ejection fraction, 65+/-9% versus 49+/-16%), hypertrophy (LV/tibia length 4.4+/-0.4 versus 5.2+/-0.6 mg/mm), interstitial fibrosis (11.2+/-3.1% versus 18.5+/-3.5%), and oxidative stress (3-fold reduction in tissue malondialdehyde). Moreover, myocyte-specific HO-1 overexpression in HF promoted tissue neovascularization and ameliorated myocardial p53 expression (2-fold reduction) and apoptosis. In isolated mitochondria, mitochondrial permeability transition was inhibited by HO-1 in a carbon monoxide (CO)-dependent manner and was recapitulated by the CO donor tricarbonylchloro(glycinato)ruthenium(II) (CORM-3). HO-1-derived CO also prevented H2O2-induced cardiomyocyte apoptosis and cell death. Finally, in vivo treatment with CORM-3 alleviated postinfarction LV remodeling, p53 expression, and apoptosis. CONCLUSIONS HO-1 induction in the failing heart is an important cardioprotective adaptation that opposes pathological LV remodeling, and this effect is mediated, at least in part, by CO-dependent inhibition of mitochondrial permeability transition and apoptosis. Augmentation of HO-1 or its product, CO, may represent a novel therapeutic strategy for ameliorating HF.
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Affiliation(s)
- Guangwu Wang
- Division of Cardiovascular Medicine, Institute of Molecular Cardiology, Department of Medicine, University of Louisville, ACB, Third Floor, 550 S Jackson St, Louisville, KY 40202, USA
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Abstract
Despite modern practices in critical care medicine, sepsis or systemic inflammatory response syndrome remains a leading cause of morbidity and mortality in the intensive care unit. Thus, the need to identify new therapeutic tools for the treatment of sepsis is urgent. In this context, carbon monoxide has become a promising therapeutic molecule that can potentially prevent uncontrolled inflammation in sepsis. In humans, carbon monoxide arises endogenously from the degradation of heme by heme oxygenase enzymes. Both endogenously synthesized and exogenously applied carbon monoxide can exert antiinflammatory and antiapoptotic effects in cells and tissues. Based on these properties, carbon monoxide, when applied at low concentration, conferred protection in a variety of cellular and rodent models of sepsis, and furthermore reduced morbidity and mortality in vivo. Therefore, application of carbon monoxide may have a major impact on the future of sepsis treatment. This review summarizes evidence for salutary effects of carbon monoxide in sepsis of various organs, including lung, heart, kidney, liver, and intestine, and discusses the potential translation of the data into human clinical trials.
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Affiliation(s)
- Alexander Hoetzel
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, The University of Pittsburgh School of Medicine, MUH 628 NW, 3459 Fifth Ave, Pittsburgh, Pennsylvania 15213, USA
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18
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Abstract
Cardiac hypertrophy and heart failure are major causes of morbidity and mortality in Western societies. Many factors have been implicated in cardiac remodeling, including alterations in gene expression in myocytes, cardiomyocytes apoptosis, cytokines and growth factors that influence cardiac dynamics, and deficits in energy metabolism as well as alterations in cardiac extracellular matrix composition. Many therapeutic means have been shown to prevent or reverse cardiac hypertrophy. New concepts for characterizing the pathophysiology of cardiac hypertrophy have been drawn from various aspects, including medical therapy and gene therapy, or use of stem cells for tissue regeneration. In this review, we focus on various types of cardiac hypertrophy, defining the causes of hypertrophy, describing available animal models of hypertrophy, discussing the mechanisms for development of hypertrophy and its transition to heart failure, and presenting the potential use of novel promising therapeutic strategies derived from new advances in basic scientific research.
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Affiliation(s)
- Sudhiranjan Gupta
- Department of Molecular Cardiology, Lerner Research Institute, The Cleveland Clinic, Cleveland, Ohio 44195, USA
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19
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Abstract
Carbon monoxide (CO) is much more than just a toxic gas. Carbon monoxide is produced endogenously by the enzyme heme oxygenase and has important functions under physiological and pathophysiological conditions. Recent studies suggested antioxidative, anti-inflammatory, antiproliferative, anti-apoptotic, and vasodilating characteristics. Regarding clinically-relevant diseases in anesthesiology and critical care medicine, such as adult respiratory distress syndrome (ARDS), sepsis, or during organ transplantation, cytoprotective properties have been demonstrated by low-dose CO in experimental models. In view of a potential CO application in future human studies, this review discusses what is known to date about CO as it relates to functional, protective and toxic aspects.
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Affiliation(s)
- A Hoetzel
- Department of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, W640 Montefiore University Hospital, 3459 Fifth Avenue, Pittsburgh PA 15213, USA.
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Coon S, Shao G, Wisel S, Vulaupalli R, Sundaram U. Mechanism of regulation of rabbit intestinal villus cell brush border membrane Na/H exchange by nitric oxide. Am J Physiol Gastrointest Liver Physiol 2007; 292:G475-81. [PMID: 17290013 DOI: 10.1152/ajpgi.00263.2005] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
In the mammalian small intestine, coupled NaCl absorption occurs via the dual operation of Na/H and Cl/HCO(3) exchange on the villus cell brush border membrane (BBM). Although constitutive nitric oxide (cNO) has been demonstrated to alter gastrointestinal tract functions, how cNO may specifically alter these two transporters to regulate coupled NaCl absorption is unknown. In villus cells, inhibition of cNO synthase (cNOS) with l-N(G)-nitroarginine methylester (l-NAME) stimulated Na/H exchange whereas Cl/HCO(3) exchange was unaffected. In villus cell BBM vesicles (BBMV) prepared from rabbits treated with l-NAME, Na/H exchange was also stimulated. d-NAME, an inactive analog of l-NAME, and N(6)-(1-imonoethyl)-l-lysine dihydrochloride, a more selective inhibitor of inducible NO synthase, did not affect Na/H exchange. Kinetic studies demonstrated that the mechanism of stimulation is secondary to an increase in the maximal rate of uptake of Na, without an alteration in the affinity of the transporter for Na. Northern blot studies demonstrated an increase in the message for the BBM Na/H exchanger NHE3, and Western blot studies showed that the immunoreactive protein levels of NHE3 was increased when cNOS was inhibited. Thus these results indicate that cNO under nominal physiological states most likely maintains an inhibitory tone on small intestinal coupled NaCl absorption by specifically inhibiting BBM Na/H expression.
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Affiliation(s)
- Steven Coon
- Section of Digestive Diseases, West Virginia Univ School of Medicine, Morgantown, WV 26506-9161, USA
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21
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Vítek L, Schwertner HA. The Heme Catabolic Pathway and its Protective Effects on Oxidative Stress‐Mediated Diseases. Adv Clin Chem 2007; 43:1-57. [PMID: 17249379 DOI: 10.1016/s0065-2423(06)43001-8] [Citation(s) in RCA: 152] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Bilirubin, the principal bile pigment, is the end product of heme catabolism. For many years, bilirubin was thought to have no physiological function other than that of a waste product of heme catabolism--useless at best and toxic at worst. Although hyperbilirubinemia in neonates has been shown to be neurotoxic, studies performed during the past decade have found that bilirubin has a number of new and interesting biochemical and biological properties. In addition, there is now a strong body of evidence suggesting that bilirubin may have a beneficial role in preventing oxidative changes in a number of diseases including atherosclerosis and cancer, as well as a number of inflammatory, autoimmune, and degenerative diseases. The results also suggest that activation of the heme oxygenase and heme catabolic pathway may have beneficiary effects on disease prevention either through the action of bilirubin or in conjunction with bilirubin. If so, it may be possible to therapeutically induce heme oxygenase, increase bilirubin concentrations, and lower the risk of oxidative stress-related diseases.
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Affiliation(s)
- Libor Vítek
- Fourth Department of Internal Medicine, Institute of Clinical Biochemistry, Laboratory Diagnostics, Charles University of Prague, U Nemocnice 2, Praha 2, 128 08 Prague, Czech Republic
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22
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Abstract
Cardiovascular abnormalities accompany both portal hypertension and cirrhosis. These consist of hyperdynamic circulation, defined as reduced mean arterial pressure and systemic vascular resistance, and increased cardiac output. Despite the baseline increased cardiac output, ventricular inotropic and chronotropic responses to stimuli are blunted, a condition known as cirrhotic cardiomyopathy. Both conditions may play an initiating or aggravating pathogenic role in many of the complications of liver failure or portal hypertension including ascites, variceal bleeding, hepatorenal syndrome and increased postoperative mortality after major surgery or liver transplantation. This review briefly examines the major mechanisms that may underlie these cardiovascular abnormalities, concentrating on nitric oxide, endogenous cannabinoids, central neural activation and adrenergic receptor changes. Future work should address the complex interrelationships between these systems.
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Affiliation(s)
- HongQun Liu
- Liver Unit, Department of Medicine, University of Calgary. 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada
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23
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Gupta S, Sen S. Role of the NF-kappaB signaling cascade and NF-kappaB-targeted genes in failing human hearts. J Mol Med (Berl) 2005; 83:993-1004. [PMID: 16133425 DOI: 10.1007/s00109-005-0691-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2005] [Accepted: 05/20/2005] [Indexed: 11/24/2022]
Abstract
Nuclear factor-kappaB (NF-kappaB) is a ubiquitous transcription factor that has been indicated to play a causal role for many pathological states. Heart failure is a major cause of morbidity all over the world. In this study, we examined the role of NF-kappaB in failing (F) human hearts and nonfailing (NF) controls. Our data showed that an enhanced activation of this nuclear factor occurs in the F hearts along with its components, like I-kappaB kinase (IKK)beta and IkappaBalpha, both at transcript and translational levels. To obtain a profile of NF-kappaB-targeted gene expression in F hearts, we profiled, for the first time, the expression analysis of NF-kappaB-linked gene using a TranSignal human NF-kappaB-targeted gene array. Our data suggest that more than 50 genes were consistently upregulated in F hearts more than 1.5-fold (vs NF hearts, p<0.001). Our studies demonstrated that NF-kappaB is specifically and significantly activated via IKKbeta in F hearts. The most intriguing aspects of our studies are molecular profiles of NF-kappaB-linked or targeted gene expression in F hearts. Our data suggest that the regulation and control of NF-kappaB activation is, therefore, a powerful therapeutic strategy for delaying or attenuating such deadly disease.
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Affiliation(s)
- Sudhiranjan Gupta
- Department of Molecular Cardiology, NB 50, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
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Seshadri N, Dweik RA, Laskowski D, Pothier C, Rodriguez L, Young JB, Migrino RQ. Dysregulation of endogenous carbon monoxide and nitric oxide production in patients with advanced ischemic or nonischemic cardiomyopathy. Am J Cardiol 2003; 92:820-3. [PMID: 14516883 DOI: 10.1016/s0002-9149(03)00890-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Carbon monoxide (CO) and nitric oxide (NO) are endogenous vasoregulatory molecules whose role in heart failure is not fully known. Exhaled CO and NO measurement provide novel noninvasive assessment of their endogenous production. We compared exhaled CO and NO in 24 patients with advanced ischemic and nonischemic cardiomyopathy and in 13 control subjects without known cardiac disease at rest and at 1 and 5 minutes after exercise testing. Exhaled CO was lower in patients with cardiomyopathy at rest (1.66 +/- 0.2 vs 1.80 +/- 0.5 ppm, p = 0.02) and 1 minute after exercise (1.35 +/- 0.2 vs 1.81 +/- 0.5 ppm, p = 0.009), with a similar trend at 5 minutes after exercise (1.45 +/- 0.3 vs 1.81 +/- 0.5 ppm, p = 0.14). Exhaled CO decreased in patients with cardiomyopathy after exercise (p <0.001 and p = 0.02 at rest vs 1 and 5 minutes after exercise, respectively) but was maintained in controls. Exhaled NO did not differ between patients with cardiomyopathy and controls at rest (9.48 +/- 1.4 vs 9.68 +/- 1.5 ppb, p = NS) and after exercise (1 minute: 10.91 +/- 1.8 vs 9.19 +/- 1.2 ppb; 5 minutes: 10.52 +/- 1.5 vs 8.90 +/- 1.2 ppb, p = NS). Exhaled NO increased after exercise in patients with cardiomyopathy (p = 0.01 and p = 0.04 rest vs exercise at 1 and 5 minutes, respectively), but was maintained in controls. Exhaled CO and NO were not correlated with peak oxygen consumption in patients with cardiomyopathy. The differential responses in exhaled CO and NO at rest or with exercise between patients with cardiomyopathy and normal controls may point to dysregulation in endogenous CO and NO production.
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Affiliation(s)
- Niranjan Seshadri
- Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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26
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Bronzwaer JGF, Heymes C, Visser CA, Paulus WJ. Myocardial fibrosis blunts nitric oxide synthase-related preload reserve in human dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 2003; 284:H10-6. [PMID: 12485814 DOI: 10.1152/ajpheart.00401.2002] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The purpose of the study was to investigate interactions between myocardial nitric oxide synthase (NOS) and myocardial fibrosis, both of which determine left ventricular (LV) preload reserve in patients with nonischemic dilated cardiomyopathy (DCM). In previous animal experiments, chronic inhibition of NOS induced myocardial fibrosis and limited LV preload reserve. Twenty-eight DCM patients underwent LV catheterization, balloon caval occlusions (BCO; n = 8), intracoronary substance P infusion (n = 8), and procurement of LV endomyocardial biopsies for determinations of collagen volume fraction (CVF), of gene expression of NOS2, NOS3, heme oxygenase (HO)-1, and TNF-alpha, and of NOS2 protein. CVF was unrelated to the intensity of NOS2, NOS3, HO-1, or TNF-alpha gene expression or of NOS2 protein expression. Preload recruitable LV stroke work (PR-LVSW) correlated directly with NOS2 gene expression (P = 0.001) and inversely with CVF (P = 0.04). High CVF (>10%) reduced baseline LVSW and PR-LVSW at each level of NOS2 gene expression. In DCM, myocardial fibrosis is unrelated to the intensity of myocardial gene expression of NOS, antioxidative enzymes (HO-1), or cytokines (TNF-alpha) and blunts NOS2-related recruitment of LV preload reserve.
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Affiliation(s)
- Jean G F Bronzwaer
- VU-University Medical Center and Institute for Cardiovascular Research-VU, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
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27
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Vulapalli SR, Chen Z, Chua BHL, Wang T, Liang CS. Cardioselective overexpression of HO-1 prevents I/R-induced cardiac dysfunction and apoptosis. Am J Physiol Heart Circ Physiol 2002; 283:H688-94. [PMID: 12124217 DOI: 10.1152/ajpheart.00133.2002] [Citation(s) in RCA: 92] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Heme oxygenase (HO)-1 converts heme to bilirubin, carbon monoxide, and iron. Our prior work has suggested a cardioprotective role for HO-1 in heart failure. To test whether HO-1 (heat shock protein 32) prevents cardiomyocyte apoptosis and cardiac dysfunction after ischemia-reperfusion (I/R), we generated transgenic mice overexpressing HO-1 in the heart under the control of the alpha-myosin heavy chain promoter. HO-1 transcript and protein increased markedly in the heart only. In an isolated heart preparation, we observed an enhanced functional recovery during reperfusion after ischemia in the transgenic hearts compared with nontransgenic controls. I/R injury was also performed in intact animals by coronary ligation and reperfusion to assess the protective role of HO-1 overexpression on heart apoptosis. HO-1 overexpression reduced cardiac apoptosis, as evidenced by fewer terminal deoxynucleodidyl transferase-mediated dUTP nick-end labeling-positive or in situ oligo ligation-positive myocytes, compared with nontransgenic mice. Our results indicate that cardioselective overexpression of HO-1 exerts a cardioprotective effect after myocardial I/R in mice, and this effect is probably mediated via an antiapoptotic action of HO-1.
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Affiliation(s)
- Sreesatya Raju Vulapalli
- Cardiology Unit, Department of Medicine, University of Rochester School of Medicine, 601 Elmwood Avenue, Rochester, NY 14642, USA.
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Abstract
Modern methods of cell and molecular biology, augmented by molecular technology, have great potential for helping to unravel the complex mechanisms of various diseases. They also have the potential to help us try to dissect the events which follow the altered physiological conditions. Thus, there is every reason to believe that some of the potential mechanisms will be translated sooner or later into the clinic. Heme oxygenase (HO)-related mechanisms play an important role in several aspects of different diseases. In the past several years, significant progress has been made in our understanding of the function and regulation of HO. The objective of this article is to review current knowledge relating to the importance of HO mechanism in various diseases including myocardial ischemia/reperfusion, hypertension, cardiomyopathy, organ transplantation, endotoxemia, lung diseases, and immunosuppression. The morbidity and mortality of these diseases remain high even with optimal medical management. Furthermore, in this review, we consider various factors influencing the HO system and finally assess current pharmacological approaches to their control.
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Affiliation(s)
- Arpad Tosaki
- Department of Pharmacology, School of Medicine, Faculty of Pharmacy, University of Debrecen, Hungary.
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29
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Vítek L, Jirsa M, Brodanová M, Kalab M, Marecek Z, Danzig V, Novotný L, Kotal P. Gilbert syndrome and ischemic heart disease: a protective effect of elevated bilirubin levels. Atherosclerosis 2002; 160:449-56. [PMID: 11849670 DOI: 10.1016/s0021-9150(01)00601-3] [Citation(s) in RCA: 307] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Oxidation processes play an important role in atherogenesis. Bilirubin IXalpha is recognised as a potent antioxidant. In the present study, we assessed the role of elevated serum bilirubin levels in the prevention of ischemic heart disease (IHD). METHODS The occurrence of IHD was determined in Gilbert syndrome (GS) patients above 40 years (n=50). The diagnosis was based on past medical history and ECG criteria. The occurrence was related to that of the comparable general population (n=2296). Serum biochemistry, including the total antioxidant status was evaluated in the GS subjects, IHD patients (n=38) and control subjects (n=38). RESULTS The prevalence of IHD in GS subjects (aged 49.7+/-9.0 years) was 2% (0.05-10.7%, 95% confidence interval), compared to 12.1% in a general population (P<0.05). Bilirubin, total antioxidant capacity and high density lipoprotein (HDL) cholesterol were found to be significantly higher in GS subjects compared to control groups (P<0.05). According to linear discriminant analysis, hyperbilirubinemia rather than elevation of HDL cholesterol levels seemed to be more important in protection from IHD. CONCLUSIONS In the present study, low prevalence of IHD in GS subjects was detected. It may be presumed that chronic hyperbilirubinemia prevent the development of IHD by increasing the serum antioxidant capacity.
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Affiliation(s)
- Libor Vítek
- 4th Department of Internal Medicine, 1st Medical Faculty, Charles University Prague, U Nemocnice 2, 128 08 Prague, Czech Republic.
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30
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Qin F, Vulapalli RS, Stevens SY, Liang CS. Loss of cardiac sympathetic neurotransmitters in heart failure and NE infusion is associated with reduced NGF. Am J Physiol Heart Circ Physiol 2002; 282:H363-71. [PMID: 11748083 DOI: 10.1152/ajpheart.00319.2001] [Citation(s) in RCA: 65] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Sympathetic neurotransmitters are diminished in cardiac efferent nerve endings in congestive heart failure (CHF). Similar changes occur after exogenous norepinephrine (NE) infusion. Since NE reduces nerve growth factor (NGF) in cultured cardiomyocytes, we proposed to determine whether the loss of noradrenergic transmitters in the failing heart is caused by the NE-mediated reduction of NGF or its neurotrophic receptor tyrosine kinase A (TrKA). Dogs were assigned to receive either rapid ventricular pacing (225 beats/min) or NE infusion (0.5 microg/kg/min) for 8 wk. Control animals received either cardiac pacing of 100 beats/min or saline infusion. We measured NGF and TrKA proteins by Western blot and immunocytochemistry and measured NGF and TrKA mRNAs by reverse transcription polymerase chain reaction, neuronal catecholaminergic histofluorescence, tyrosine hydroxylase-immunostained profiles, and plasma NE. Rapid ventricular pacing produced CHF with increased plasma NE, decreased myocardial NGF protein (0.61 +/- 0.07 vs. 1.04 +/- 0.04, P < 0.05), TrKA protein (0.75 +/- 0.08 vs. 0.98 +/- 0.06, P < 0.05), NGF and TrKA mRNAs and reduced catecholaminergic histofluorescence (197 +/- 23 vs. 485 +/- 43, P < 0.05), and tyrosine hydroxylase profiles (360 +/- 51 vs. 773 +/- 36, P < 0.05). Decreases in tissue NGF and TrKA protein were also noted by immunocytochemistry. Similar changes occurred in NE-treated animals. Tissue NGF and TrKA levels correlated closely with the noradrenergic transmitter profiles. We conclude that cardiac NGF and TrKA are reduced by rapid ventricular pacing and NE infusion, and that these changes correlate with decreases of cardiac catecholaminergic and tyrosine hydroxylase profiles. Findings indicate that decrease of cardiac sympathetic transmitters in heart failure is associated with NE-mediated reduction of NGF and TrKA.
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Affiliation(s)
- Fuzhong Qin
- Department of Medicine, University of Rochester Medical Center, 601 Elmwood Ave., Rochester, NY 14642, USA
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Liu H, Song D, Lee SS. Role of heme oxygenase-carbon monoxide pathway in pathogenesis of cirrhotic cardiomyopathy in the rat. Am J Physiol Gastrointest Liver Physiol 2001; 280:G68-74. [PMID: 11123199 DOI: 10.1152/ajpgi.2001.280.1.g68] [Citation(s) in RCA: 67] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The enzyme heme oxygenase (HO), which exists in inducible (HO-1) and constitutive (HO-2) isoforms, degrades heme to biliverdin and CO. CO depresses cardiac contraction via cGMP. We aimed to clarify a possible role for the HO-CO pathway in the pathogenesis of cirrhotic cardiomyopathy in bile duct-ligated rats. Four weeks after bile duct ligation or sham operation, rat ventricles were examined for HO-1 and HO-2 mRNA by RT-PCR and for protein expression by Western blotting. Total HO enzyme activity and cGMP levels were also measured. The effects of a HO inhibitor, zinc protoporphyrin IX (ZnPP), on ventricular cGMP levels and isolated papillary muscle contractility were studied. We found that HO-1 mRNA transcription and protein expression were significantly augmented in cirrhotic hearts compared with sham-operated controls, whereas there was no difference in HO-2 mRNA or protein levels. Total HO activity and cGMP levels were significantly increased in cirrhotic ventricles vs. controls. In cirrhotic ventricles, treatment with ZnPP significantly decreased cGMP production and improved the blunted papillary muscle contractility, whereas it had no effect on control muscles. CO perfusion inhibited papillary muscle contractility, an effect completely blocked by methylene blue and partially blocked by ZnPP. These results indicate that activation of the HO-CO-cGMP pathway is involved in the pathogenesis of cirrhotic cardiomyopathy.
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Affiliation(s)
- H Liu
- Liver Unit, University of Calgary, Calgary, Alberta, Canada
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Abstract
Heme oxygenase (HO)-1 is the inducible isoform of the rate-limiting enzyme of heme degradation. HO regulates the cellular content of the pro-oxidant heme and produces catabolites with physiological functions. HO-1 is induced by a host of oxidative stress stimuli, and the activation of HO-1 gene expression is considered to be an adaptive cellular response to survive exposure to environmental stresses. Since overexpression of the HO-1 gene is also protective against the deleterious effects of experimental injuries, the specific induction of HO-1 by 'non-stressful' stimuli, eg. stimuli that are not associated with oxidative stress, such as adenosine 3', 5'-cyclic monophosphate or cyclic guanosine 3',5'-monophosphate, may have important clinical implications. This review summarizes recent advances in the understanding of regulatory mechanisms of HO-1 gene expression, in particular the role of various redox-dependent and redox-independent signaling pathways. Models of experimental injuries are highlighted in which specific overexpression of the HO-1 gene either by targeted gene transfer or by pharmacological modulation has been demonstrated to provide therapeutic effects.
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Affiliation(s)
- S Immenschuh
- Zentrum Innere Medizin, Abteilung Gastroenterologie und Endokrinologie, Georg-August-Universität, Göttingen, Germany.
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