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Polysulfides Link H2S to Protein Thiol Oxidation

机译:多硫化物将H2S连接到蛋白质硫醇氧化

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摘要

>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. Antioxid. Redox Signal. 19, 1749–1765.
机译:>目的:建议硫化氢(H2S)在多种生理过程中起气体信号分子的作用。有人提出其作用机理涉及蛋白质S的巯基化作用,即半胱氨酸硫醇盐(Cys-S -)转化为过硫化物(Cys-S-S -)。一个尚未解决的核心问题是,H2S(即具有处于最低可能氧化态(-2)的硫的分子)如何导致氧化硫醇修饰。 >结果:使用脂质磷酸酶PTEN作为模型蛋白,我们发现“ H2S供体”氢硫化钠(NaHS)导致该酶在体外的快速可逆氧化。我们确定在NaHS溶液中形成的多硫化物为氧化性物质,并提供证据表明硫磺硫被添加到了活性位点的半胱氨酸中。所有测试的“硫化氢供体”都诱导了多硫化物介导的PTEN氧化,包括硫化钠(Na2S),气态硫化氢和吗啉-4-鎓4-甲氧基苯基(吗啉代)次膦酸二硫代酯(GYY4137)。而且,我们表明在H2S溶液中形成的多硫化物很容易修饰完整细胞内部的PTEN。 >创新:我们的结果揭示了以前尚未解决的有关H2S如何导致蛋白质硫醇氧化的问题,并表明在H2S溶液中形成的多硫化物介导了这一过程。 >结论:这项研究表明,先前报告中归因于H2S的影响实际上可能是由多硫化物介导的。它还支持以下观点:硫磺而不是硫化物是H2S信号传导的实际体内媒介。抗氧化。氧化还原信号。 19,1749–1765。

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