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 language | English |
|---|---|
| Pages (from-to) | 714-724 |
| Number of pages | 11 |
| Journal | Nature Chemical Biology |
| Volume | 8 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2012 Aug |
Fingerprint
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
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 journal › Article
}
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.
UR - http://www.scopus.com/inward/record.url?scp=84864284437&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864284437&partnerID=8YFLogxK
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 -