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H2S Signals Through Protein S-Sulfhydration

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TLDR
Ex vivo endogenous H2S physiologically modifies cysteine residues in many proteins, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and actin, converting Cysteine -SH groups to -SSH groups in a process the authors call S-sulfhydration.
Abstract
Hydrogen sulfide (H2S), a messenger molecule generated by cystathionine gamma-lyase, acts as a physiologic vasorelaxant. Mechanisms whereby H2S signals have been elusive. We now show that H2S physiologically modifies cysteines in a large number of proteins by S-sulfhydration. About 10 to 25% of many liver proteins, including actin, tubulin, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), are sulfhydrated under physiological conditions. Sulfhydration augments GAPDH activity and enhances actin polymerization. Sulfhydration thus appears to be a physiologic posttranslational modification for proteins.

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Journal ArticleDOI

Redox Signaling Regulated by Cysteine Persulfide and Protein Polysulfidation.

TL;DR: Elucidation of the redox signaling regulatory mechanism of reactive persulfide species including small thiol molecules and thiol-containing proteins should lead to the development of new therapeutic strategies and drug discoveries for oxidative and electrophilic stress-related diseases.
Journal ArticleDOI

S-sulfhydration/desulfhydration and S-nitrosylation/denitrosylation: A Common Paradigm for Gasotransmitter Signaling by H2S and NO

TL;DR: Proteomic methods for studying H2S-dependent S-sulfhydration suggest that this is also an abundant modification with potential for global physiological importance, and similarities with S-nitrosylated/denitrosylation are compared.
Journal ArticleDOI

Homocysteine and hydrogen sulfide in epigenetic, metabolic and microbiota related renovascular hypertension.

TL;DR: Recent advances in the field of hypertension research emphasizing renal contribution and how H2S physiology can be exploited as a possible therapeutic strategy to ameliorate kidney dysfunction as well as to control blood pressure are summarized.
Journal ArticleDOI

Negative Regulation of Autophagy by Sulfide Is Independent of Reactive Oxygen Species

TL;DR: New experimental evidence is provided that sulfide was unable to scavenge reactive oxygen species generated by nitrogen limitation, in contrast to well-established reducers, and reducers were unable to inhibit the accumulation of autophagic bodies and ATG8 protein forms to the same extent as sulfide.
Journal ArticleDOI

Abscisic Acid-Triggered Persulfidation of the Cys Protease ATG4 Mediates Regulation of Autophagy by Sulfide.

TL;DR: The data strongly suggest that the negative regulation of autophagy by sulfide is mediated by specific persulfidation of the ATG4 protease.
References
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Journal ArticleDOI

H2S as a Physiologic Vasorelaxant: Hypertension in Mice with Deletion of Cystathionine γ-Lyase

TL;DR: It is shown that H2S is physiologically generated by cystathionine γ-lyase (CSE) and that genetic deletion of this enzyme in mice markedly reduces H 2S levels in the serum, heart, aorta, and other tissues.
Journal ArticleDOI

Protein S-nitrosylation: purview and parameters.

TL;DR: S-nitrosylation conveys a large part of the ubiquitous influence of nitric oxide on cellular signal transduction, and provides a mechanism for redox-based physiological regulation.
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The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener

TL;DR: It is demonstrated that H2S is an important endogenous vasoactive factor and the first identified gaseous opener of KATP channels in vascular SMCs and production from vascular tissues was enhanced by nitric oxide.
Journal ArticleDOI

Hydrogen sulphide and its therapeutic potential

TL;DR: The physiology and biochemistry of H2S is overviews, the effects of H 2S inhibitors or H2s donors in animal models of disease are summarized, the potential options for the therapeutic exploitation of H1S are outlined and they are outlined.
Journal ArticleDOI

Protein S-nitrosylation: a physiological signal for neuronal nitric oxide.

TL;DR: Protein S-nitrosylation is established as a physiological signalling mechanism for neuronally generated NO in mice harbouring a genomic deletion of neuronal NO synthase (nNOS).
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