Document Detail

Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration.
MedLine Citation:
PMID:  22772154     Owner:  NLM     Status:  MEDLINE    
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.
Motohiro Nishida; Tomohiro Sawa; Naoyuki Kitajima; Katsuhiko Ono; Hirofumi Inoue; Hideshi Ihara; Hozumi Motohashi; Masayuki Yamamoto; Makoto Suematsu; Hitoshi Kurose; Albert van der Vliet; Bruce A Freeman; Takahiro Shibata; Koji Uchida; Yoshito Kumagai; Takaaki Akaike
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-01
Journal Detail:
Title:  Nature chemical biology     Volume:  8     ISSN:  1552-4469     ISO Abbreviation:  Nat. Chem. Biol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2012-11-05     Revised Date:  2014-08-10    
Medline Journal Info:
Nlm Unique ID:  101231976     Medline TA:  Nat Chem Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  714-24     Citation Subset:  IM    
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MeSH Terms
Cell Line
Cell Membrane
Cyclic GMP / analogs & derivatives,  chemistry,  metabolism
Gene Expression Regulation
Genes, ras / physiology
Hydrogen Sulfide / chemistry*,  metabolism*
Mice, Inbred C57BL
Molecular Structure
Myocytes, Cardiac / metabolism
RNA Interference
Signal Transduction / physiology*
Grant Support
Reg. No./Substance:
0/8-nitroguanosine 3',5'-cyclic monophosphate; 0/Anions; H2D2X058MU/Cyclic GMP; YY9FVM7NSN/Hydrogen Sulfide

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