Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration.
Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration.
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硫化氢阴离子通过亲电硫化来调节氧化还原信号传导。
DOI：
10.1038/nchembio.1018
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发表时间：
2012-08
影响因子：
14.8
通讯作者：
中科院分区：
文献类型：
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作者：
氧化还原信号传导的一个新兴方面是由亲电副产物介导的途径，所述亲电副产物例如硝化的环核苷酸（例如，8-硝基鸟苷3′，5 ′-环单磷酸（8-硝基-cGMP））和不饱和脂肪酸的硝基或酮衍生物，其通过炎症相关酶、活性氧物质、一氧化氮和次级产物的反应产生。在这里，我们报告酶促产生的硫化氢阴离子（HS-）调节各种亲电体的代谢和信号传导作用。HS−与亲电体反应，最好的代表是8-nitro-cGMP，通过直接巯基化和调节细胞氧化还原信号。心肌梗死后小鼠心脏组织中显著的8-硝基-cGMP形成加强了该反应的相关性，该8-硝基-cGMP形成受到HS−生物合成改变的调节。反过来，心脏HS-抑制亲电介导的H-Ras激活和心脏细胞衰老，有助于HS-对心肌梗死相关心力衰竭的有益作用。因此，这项研究揭示了HS-诱导的亲电体硫水合作用是调节亲电体介导的氧化还原信号的独特机制。
An emerging aspect of redox signaling is the pathway mediated by electrophilic byproducts, such as nitrated cyclic nucleotide (for example, 8-nitroguanosine 3′,5′-cyclic monophosphate (8-nitro-cGMP)) and nitro or keto derivatives of unsaturated fatty acids, generated via reactions of inflammation-related enzymes, reactive oxygen species, nitric oxide and secondary products. Here we report that enzymatically generated hydrogen sulfide anion (HS−) regulates the metabolism and signaling actions of various electrophiles. HS− reacts with electrophiles, best represented by 8-nitro-cGMP, via direct sulfhydration and modulates cellular redox signaling. The relevance of this reaction is reinforced by the significant 8-nitro-cGMP formation in mouse cardiac tissue after myocardial infarction that is modulated by alterations in HS− biosynthesis. Cardiac HS−, in turn, suppresses electrophile-mediated H-Ras activation and cardiac cell senescence, contributing to the beneficial effects of HS− on myocardial infarction–associated heart failure. Thus, this study reveals HS−-induced electrophile sulfhydration as a unique mechanism for regulating electrophile-mediated redox signaling.