Hydrogen sulfide cytoprotective signaling is endothelial nitric oxide synthase-nitric oxide dependent.

Abstract

Previous studies have demonstrated that hydrogen sulfide (H2S) protects against multiple cardiovascular disease states in a similar manner as nitric oxide (NO). H2S therapy also has been shown to augment NO bioavailability and signaling. The purpose of this study was to investigate the impact of H2S deficiency on endothelial NO synthase (eNOS) function, NO production, and ischemia/reperfusion (I/R) injury. We found that mice lacking the H2S-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 H2S therapy restored eNOS function and NO bioavailability and attenuated I/R injury. In addition, we found that H2S therapy fails to protect against I/R in eNOS phosphomutant mice (S1179A). Our results suggest that H2S-mediated cytoprotective signaling in the setting of I/R injury is dependent in large part on eNOS activation and NO generation.

• Authors: Adrienne L King, David J Polhemus, Shashi Bhushan, Hiroyuki Otsuka, Kazuhisa Kondo, Chad K Nicholson, Jessica M Bradley, Kazi N Islam, John W Calvert, Ya-Xiong Tao, Tammy R Dugas, Eric E Kelley, John W Elrod, Paul L Huang, Rui Wang, David J Lefer
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 111 Issue 8 Pg. 3182-7 (Feb 25 2014) ISSN: 1091-6490 [Electronic] United States
• PMID: 24516168 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Troponin I
• Nitric Oxide
• Nitric Oxide Synthase Type III
• Aspartate Aminotransferases
• Alanine Transaminase
• Cystathionine gamma-Lyase
• Hydrogen Sulfide

Topics

• Alanine Transaminase (blood)
• Analysis of Variance
• Animals
• Aspartate Aminotransferases (blood)
• Blotting, Western
• Chromatography, High Pressure Liquid
• Cystathionine gamma-Lyase (genetics)
• Cytoprotection (drug effects, physiology)
• Hydrogen Sulfide (metabolism, pharmacology)
• Immunohistochemistry
• Mice
• Mice, Knockout
• Mitochondria (physiology)
• Myocardial Reperfusion Injury (drug therapy, metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (metabolism)
• Oxidative Stress (physiology)
• Oxygen Consumption (physiology)
• Signal Transduction (physiology)
• Troponin I (metabolism)