Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration

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

Research output: Contribution to journalArticle

172 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)714-724
Number of pages11
JournalNature Chemical Biology
Volume8
Issue number8
DOIs
Publication statusPublished - 2012 Aug

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Hydrogen Sulfide
Oxidation-Reduction
Anions
Myocardial Infarction
Cell Aging
Cyclic Nucleotides
Unsaturated Fatty Acids
Reactive Oxygen Species
Nitric Oxide
Heart Failure
Inflammation
8-nitroguanosine 3',5'-cyclic monophosphate
Enzymes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Nishida, M., Sawa, T., Kitajima, N., Ono, K., Inoue, H., Ihara, H., ... Akaike, T. (2012). Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration. Nature Chemical Biology, 8(8), 714-724. https://doi.org/10.1038/nchembio.1018

Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration. / Nishida, Motohiro; 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.

In: Nature Chemical Biology, Vol. 8, No. 8, 08.2012, p. 714-724.

Research output: Contribution to journalArticle

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 2012, 'Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration', Nature Chemical Biology, vol. 8, no. 8, pp. 714-724. https://doi.org/10.1038/nchembio.1018
Nishida, Motohiro ; 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. / Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration. In: Nature Chemical Biology. 2012 ; Vol. 8, No. 8. pp. 714-724.
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