Protein S‐sulfhydration by hydrogen sulfide in cardiovascular system

Meng, Guoliang; Zhao, Shuang; Xie, Liping; Han, Yi; Ji, Yong

doi:10.1111/bph.13825

Cited by 89 publications

(64 citation statements)

References 87 publications

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“…In the last years, it is becoming increasingly clear that also protein S-sulfuration [19] represents an important mechanism of regulation of protein activity mediated by hydrogen sulfide (H 2 S) ( Figure 1). In this respect, it has been reported that these modifications occur on enzymes, receptors, transcription factors, and ion channels and represent key regulatory events in maintaining the physiological function of proteins in the cardiovascular system [20]. Among the abovementioned reversible reactions, protein S-thiolation by LMW thiols is the most biologically…”

Section: Protein Sulfhydryls Oxidation and Atherosclerosismentioning

confidence: 99%

Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation

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2020

Oxidative Medicine and Cellular Longevity

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Although oxidative stress has been long associated with the genesis and progression of the atherosclerotic plaque, scanty data on its in situ effects on protein sulfhydryl group modifications are available. Within the arterial wall, protein sulfhydryls and low-molecular-weight (LMW) thiols are involved in the cell regulation of both Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) levels and are a target for several posttranslational oxidative modifications that take place inside the atherosclerotic plaque, probably contributing to both atherogenesis and atherosclerotic plaque progression towards complicated lesions. Advanced carotid plaques are characterized by very high intraplaque GSH levels, due to cell lysis during apoptotic and/or necrotic events, probably responsible for the altered equilibrium among protein sulfhydryls and LMW thiols. Some lines of evidence show that the prooxidant environment present in atherosclerotic tissue could modify filtered proteins also by protein-SH group oxidation, and demonstrate that particularly albumin, once filtered, represents a harmful source of homocysteine and cysteinylglycine inside the plaque. The oxidative modification of protein sulfhydryls, with particular emphasis to protein thiolation by LMW thiols and its association with atherosclerosis, is the main topic of this review.

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Section: Protein Sulfhydryls Oxidation and Atherosclerosismentioning

confidence: 99%

Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation

Lepedda

Formato

2020

Oxidative Medicine and Cellular Longevity

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“…S-sulfhydration was performed as described previously (Meng, Zhao, Xie, Han, & Ji, 2018). Briefly, NRCMs or heart tissues were homogenized in HEN buffer (composition; 250-mM HEPES-NaOH, pH 7.7: 1-mM EDTA; 0.1-mM neocuproine), supplemented with 100-mM deferoxamine and centrifuged at 13,000× g for 30 min at 4°C.…”

Section: S-sulfhydration Assaymentioning

confidence: 99%

Hydrogen sulfide regulates muscle RING finger‐1 protein S‐sulfhydration at Cys⁴⁴ to prevent cardiac structural damage in diabetic cardiomyopathy

Sun

Zhao

et al. 2019

British J Pharmacology

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Background and Purpose Hydrogen sulfide (H2S) plays important roles as a gasotransmitter in pathologies. Increased expression of the E3 ubiquitin ligase, muscle RING finger‐1 (MuRF1), may be involved in diabetic cardiomyopathy. Here we have investigated whether and how exogenous H2S alleviates cardiac muscle degradation through modifications of MuRF1 S‐sulfhydration in db/db mice. Experimental Approach Neonatal rat cardiomyocytes were treated with high glucose (40 mM), oleate (100 μM), palmitate (400 μM), and NaHS (100 μM) for 72 hr. MuRF1 was silenced with siRNA technology and mutation at Cys44. Endoplasmic reticulum stress markers, MuRF1 expression, and ubiquitination level were measured. db/db mice were injected with NaHS (39 μmol·kg−1) for 20 weeks. Echocardiography, cardiac ultrastructure, cystathionine‐γ‐lyase, cardiac structure proteins expression, and S‐sulfhydration production were measured. Key Results H2S levels and cystathionine‐γ‐lyase protein expression in myocardium were decreased in db/db mice. Exogenous H2S reversed endoplasmic reticulum stress, including impairment of the function of cardiomyocytes and structural damage in db/db mice. Exogenous H2S could suppress the levels of myosin heavy chain 6 and myosin light chain 2 ubiquitination in cardiac tissues of db/db mice, and MuRF1 was modified by S‐sulfhydration, following treatment with exogenous H2S, to reduce the interaction between MuRF1 and myosin heavy chain 6 and myosin light chain 2. Conclusions and Implications Our findings suggest that H2S regulates MuRF1 S‐sulfhydration at Cys44 to prevent myocardial degradation in the cardiac tissues of db/db mice. Linked Articles This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc

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“…H2S has been recently demonstrated to posttranslational modification of proteins by the formation of a persulfide (-SSH) bond with the reactive cysteine residues of target proteins, termed as Ssulfhydration. After S-sulfhydration, proteins change their original function, serving as important switchers or regulators [48]. It is important to note that H2S induces Ssulfhydration on cysteine thiols under oxidation conditions.…”

Section: Discussionmentioning

confidence: 99%

Exogenous H2S Promoted USP8 Sulfhydration to Regulate Mitophagy in the Hearts of db/db Mice

Sun

et al. 2020

Aging and disease

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Hydrogen sulfide (H2S), an important gasotransmitter, regulates cardiovascular functions. Mitochondrial damage induced by the overproduction of reactive oxygen species (ROS) results in myocardial injury with a diabetic state. The purpose of this study was to investigate the effects of exogenous H2S on mitophagy formation in diabetic cardiomyopathy. In this study, we found that exogenous H2S could improve cardiac functions, reduce mitochondrial fragments and ROS levels, enhance mitochondrial respiration chain activities and inhibit mitochondrial apoptosis in the hearts of db/db mice. Our results showed that exogenous H2S facilitated parkin translocation into mitochondria and promoted mitophagy formation in the hearts of db/db mice. Our studies further revealed that the ubiquitination level of cytosolic parkin was increased and the expression of USP8, a deubiquitinating enzyme, was decreased in db/db cardiac tissues. S-sulfhydration is a novel posttranslational modification of specific cysteine residues on target proteins by H2S. Our results showed that the S-sulfhydration level of USP8 was obviously decreased in vivo and in vitro under hyperglycemia and hyperlipidemia, however, exogenous H2S could reverse this effect and promote USP8/parkin interaction. Dithiothreitol, a reducing agent that reverses sulfhydration-mediated covalent modification, increased the ubiquitylation level of parkin, abolished the effects of exogenous H2S on USP8 deubiquitylation and suppressed the interaction of USP8 with parkin in neonatal rat cardiomyocytes treated with high glucose, oleate and palmitate. Our findings suggested that H2S promoted mitophagy formation by increasing S-sulfhydration of USP8, which enhanced deubiquitination of parkin through the recruitment of parkin in mitochondria.

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Protein S‐sulfhydration by hydrogen sulfide in cardiovascular system

Abstract: This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

Cited by 89 publications

References 87 publications

Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation

Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation

Hydrogen sulfide regulates muscle RING finger‐1 protein S‐sulfhydration at Cys⁴⁴ to prevent cardiac structural damage in diabetic cardiomyopathy

Exogenous H2S Promoted USP8 Sulfhydration to Regulate Mitophagy in the Hearts of db/db Mice

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Protein S‐sulfhydration by hydrogen sulfide in cardiovascular system

Abstract: This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

Cited by 89 publications

References 87 publications

Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation

Oxidative Modifications in Advanced Atherosclerotic Plaques: A Focus on In Situ Protein Sulfhydryl Group Oxidation

Hydrogen sulfide regulates muscle RING finger‐1 protein S‐sulfhydration at Cys44 to prevent cardiac structural damage in diabetic cardiomyopathy

Exogenous H2S Promoted USP8 Sulfhydration to Regulate Mitophagy in the Hearts of db/db Mice

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Hydrogen sulfide regulates muscle RING finger‐1 protein S‐sulfhydration at Cys⁴⁴ to prevent cardiac structural damage in diabetic cardiomyopathy