Polysulfides link H2S to protein thiol oxidation.

doi:10.1089/ars.2012.5041

Paper

Polysulfides link H2S to protein thiol oxidation.

Published Nov 20, 2013 · R. Greiner, Z. Pálinkás, Katrin Bäsell

Antioxidants & redox signaling

Q1 SJR score

404

Citations

15

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Abstract

AIMS Hydrogen sulfide (H2S) is suggested to act as a gaseous signaling molecule in a variety of physiological processes. Its molecular mechanism of action was proposed to involve protein S-sulfhydration, that is, conversion of cysteinyl thiolates (Cys-S(-)) to persulfides (Cys-S-S(-)). A central and unresolved question is how H2S-that is, a molecule with sulfur in its lowest possible oxidation state (-2)-can lead to oxidative thiol modifications. RESULTS Using the lipid phosphatase PTEN as a model protein, we find that the "H2S donor" sodium hydrosulfide (NaHS) leads to very rapid reversible oxidation of the enzyme in vitro. We identify polysulfides formed in NaHS solutions as the oxidizing species, and present evidence that sulfane sulfur is added to the active site cysteine. Polysulfide-mediated oxidation of PTEN was induced by all "H2S donors" tested, including sodium sulfide (Na2S), gaseous H2S, and morpholin-4-ium 4-methoxyphenyl(morpholino) phosphinodithioate (GYY4137). Moreover, we show that polysulfides formed in H2S solutions readily modify PTEN inside intact cells. INNOVATION Our results shed light on the previously unresolved question of how H2S leads to protein thiol oxidation, and suggest that polysulfides formed in solutions of H2S mediate this process. CONCLUSION This study suggests that the effects that have been attributed to H2S in previous reports may in fact have been mediated by polysulfides. It also supports the notion that sulfane sulfur rather than sulfide is the actual in vivo agent of H2S signaling.

In Vitro Study

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Polysulfides formed in hydrogen sulfide solutions mediate the oxidative thiol modifications in proteins, suggesting sulfane sulfur is the actual in vivo agent of H2S signaling.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Polysulfides link H2S to protein thiol oxidation.

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References

The gasotransmitter hydrogen sulfide induces nrf2-target genes by inactivating the keap1 ubiquitin ligase substrate adaptor through formation of a disulfide bond between cys-226 and cys-613.

Hydrogen sulfide activates Nrf2 to protect cells from oxidative stress by inactivating Keap1 and regulating antioxidant genes, suggesting a feedback loop between Nrf2 and H2S.

Polysulfides are possible H2S‐derived signaling molecules in rat brain

Polysulfides are potential H2S-derived signaling molecules that stimulate TRP channels in the rat brain, causing calcium influx through activation of TRPA1 channels.

Hydrogen sulfide protects against cellular senescence via S-sulfhydration of Keap1 and activation of Nrf2.

Hydrogen sulfide protects against cellular aging by reducing oxidative stress and activating Nrf2 to counteract cellular senescence.

H2S signalling through protein sulfhydration and beyond

H2S signaling through protein sulfhydration plays a crucial role in regulating inflammation, endoplasmic reticulum stress signaling, and vascular tension in mammals.

A practical look at the chemistry and biology of hydrogen sulfide.

Hydrogen sulfide (H(2)S) is a biologically relevant signaling molecule with potential therapeutic applications, but critical understanding of practical aspects is crucial for accurate conclusions and future experiments.

Citations

Role of 3-mercaptopyruvate sulfurtransferase in cancer: Molecular mechanisms and therapeutic perspectives

3-MST plays a role in tumorigenesis and development, and its inhibition may have potential for tumor therapy.

Probing Deep Hydrogen Polysulfides Fluctuations In Vivo by Engineering Activatable Fluorescence Reporters with Second Near-Infrared Window Emission.

This study developed an activatable NIR-II probe for specific and deep imaging of H2Sn, enabling accurate identification of acute inflammation in animal models.

Polysulfide and persulfide-mediated activation of the PERK-eIF2α-ATF4 pathway increases Sestrin2 expression and reduces methylglyoxal toxicity

Polysulfides and persulfides activate the PERK-eIF2-ATF4 pathway, which protects neuronal cells from methylglyoxal toxicity, offering potential new therapeutic strategies.

Understanding Polysulfide-Mediated Papain Inhibition and Differentiating between Disulfide vs Persulfide Formation.

Polysulfides effectively inhibit papain protein and can be differentiated between persulfidation and disulfide formation using TXPTS.

Phototriggered Hydrogen Persulfide Donors via Hydrosulfide Radical Formation Enhancing the Reactive Sulfur Metabolome in Cells.

Tertiary naphthacyl thiols can effectively release hydrogen persulfide (H2S2) through hydrosulfide radical formation, offering a stable and spatiotemporal controllable tool for research on sulfur metabolism in cells.

Protein persulfidation in plants: mechanisms and functions beyond a simple stress response.

Protein persulfidation in plants plays a crucial role in maintaining mitochondrial bioenergetic processes and regulating protein function.

Development of a Bioorthogonal Click-to-Release Reaction for Hydrogen Polysulfide (H2Sn) Detection.

This study developed a bioorthogonal click-to-release reaction for selective H2Sn detection in living cells, enabling further biological studies on H2Sn.