1. Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent.
- Author
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King, Adrienne L., Polhemus, David J., Bhushan, Shashi, Otsuka, Hiroyuki, Kondo, Kazuhisa, Nicholson, Chad K., Bradley, Jessica M., Islam, Kazi N., Calvert, John W., Ya-Xiong Tao, Dugas, Tammy R., Kelley, Eric E., Elrod, John W., Huang, Paul L., Rui Wang, and Lefer, David J.
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HYDROGEN sulfide ,CARDIOVASCULAR diseases ,CYSTATHIONINE ,BIOAVAILABILITY ,BIOCHEMISTRY - Abstract
Previous studies have demonstrated that hydrogen sulfide (H
2 S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO). H2 S therapy also has been shown to augment NO bioavailability and signaling. The purpose of this study was to investigate the impact of H2 S deficiency on endothelial NO synthase (eNOS) function, NO production, and ischemia/reperfusion (I/R) injury. We found that mice lacking the H2 S-producing enzyme cystathionine γ-lyase (CSE) exhibit elevated oxidative stress, dysfunctional eNOS, diminished NO levels, and exacerbated myocardial and hepatic I/R injury. In CSE KO mice, acute H2 S therapy restored eNOS function and NO bioavailability and attenuated I/R injury. In addition, we found that H2 S therapy fails to protect against I/R in eNOS phosphomutant mice (S1179A). Our results suggest that H2 S-mediated cytoprotective signaling in the setting of I/R injury is dependent in large part on eNOS activation and NO generation. [ABSTRACT FROM AUTHOR]- Published
- 2014
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