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PMID: 22772154 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration.

Nature chemical biology ·Vol. 8 ·No. 8 ·2012-08-00 ·Pages 714-24

Nishida M, Sawa T, Kitajima N, Ono K, Inoue H, Ihara H, Motohashi H, Yamamoto M, Suematsu M, Kurose H, van der Vliet A, Freeman BA, Shibata T, Uchida K, Kumagai Y, Akaike T

Abstract

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.

MeSH Terms
Animals Anions Cell Line Cell Membrane Cyclic GMP/analogs & derivatives,chemistry,metabolism Gene Expression Regulation Genes, ras/physiology Humans Hydrogen Sulfide/chemistry,metabolism Male Mice Mice, Inbred C57BL Molecular Structure Myocytes, Cardiac/metabolism Oxidation-Reduction RNA Interference Rats Signal Transduction/physiology
Chemicals
8-nitroguanosine 3',5'-cyclic monophosphate Anions Cyclic GMP Hydrogen Sulfide
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Nishida Motohiro
Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Sawa Tomohiro
Kitajima Naoyuki
Ono Katsuhiko
Inoue Hirofumi
Ihara Hideshi
Motohashi Hozumi
Yamamoto Masayuki
Suematsu Makoto
Kurose Hitoshi
van der Vliet Albert
Freeman Bruce A
Shibata Takahiro
Uchida Koji
Kumagai Yoshito
Akaike Takaaki
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Article Info
Journal
Nature chemical biology
Abbr.
Nat Chem Biol
ISSN
1552-4469
DOI
10.1038/nchembio.1018
Published
2012-08-00
Epub
2012-00-01
Pages
714-24
Language
English
Region
United States
NLM ID
101231976
PMCID
PMC4123552
Subset
IM
Grants
NHLBI NIH HHS · R01 HL132550 · United States
NHLBI NIH HHS · R01 HL058115 · United States
NHLBI NIH HHS · R01 HL064937 · United States
NHLBI NIH HHS · R01 HL085646 · United States
NIEHS NIH HHS · R01 ES021476 · United States
External Links
PubMed source DOI: 10.1038/nchembio.1018 PMC Full Text View journal details
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