TY - JOUR
T1 - Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration
AU - Nishida, Motohiro
AU - Sawa, Tomohiro
AU - Kitajima, Naoyuki
AU - Ono, Katsuhiko
AU - Inoue, Hirofumi
AU - Ihara, Hideshi
AU - Motohashi, Hozumi
AU - Yamamoto, Masayuki
AU - Suematsu, Makoto
AU - Kurose, Hitoshi
AU - Van Der Vliet, Albert
AU - Freeman, Bruce A.
AU - Shibata, Takahiro
AU - Uchida, Koji
AU - Kumagai, Yoshito
AU - Akaike, Takaaki
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
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U2 - 10.1038/nchembio.1018
DO - 10.1038/nchembio.1018
M3 - Article
C2 - 22772154
AN - SCOPUS:84864284437
VL - 8
SP - 714
EP - 724
JO - Nature Chemical Biology
JF - Nature Chemical Biology
SN - 1552-4450
IS - 8
ER -