Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration.

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.

• Authors: 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
• Journal: Nature chemical biology (Nat Chem Biol) Vol. 8 Issue 8 Pg. 714-24 (Aug 2012) ISSN: 1552-4469 [Electronic] United States
• PMID: 22772154 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 8-nitroguanosine 3',5'-cyclic monophosphate
• Anions
• Cyclic GMP
• Hydrogen Sulfide

Topics

• 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)