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Biochim Biophys Acta. 2012 Jun;1820(6):752-62. doi: 10.1016/j.bbagen.2011.04.002. Epub 2011 Apr 16.

Regulation of cardiovascular cellular processes by S-nitrosylation.

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  • 1Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA.

Abstract

BACKGROUND:

Nitric oxide (NO), a highly versatile signaling molecule, exerts a broad range of regulatory influences in the cardiovascular system that extends from vasodilation to myocardial contractility, angiogenesis, inflammation, and energy metabolism. Considerable attention has been paid to deciphering the mechanisms for such diversity in signaling. S-nitrosylation of cysteine thiols is a major signaling pathway through which NO exerts its actions. An emerging concept of NO pathophysiology is that the interplay between NO and reactive oxygen species (ROS), the nitroso/redox balance, is an important regulator of cardiovascular homeostasis.

SCOPE OF REVIEW:

ROS react with NO, limit its bioavailability, and compete with NO for binding to the same thiol in effector molecules. The interplay between NO and ROS appears to be tightly regulated and spatially confined based on the co-localization of specific NO synthase (NOS) isoforms and oxidative enzymes in unique subcellular compartments. NOS isoforms are also in close contact with denitrosylases, leading to crucial regulation of S-nitrosylation.

MAJOR CONCLUSIONS:

Nitroso/redox balance is an emerging regulatory pathway for multiple cells and tissues, including the cardiovascular system. Studies using relevant knockout models, isoform specific NOS inhibitors, and both in vitro and in vivo methods have provided novel insights into NO- and ROS-based signaling interactions responsible for numerous cardiovascular disorders.

GENERAL SIGNIFICANCE:

An integrated view of the role of nitroso/redox balance in cardiovascular pathophysiology has significant therapeutic implications. This is highlighted by human studies where pharmacologic manipulation of oxidative and nitrosative pathways exerted salutary effects in patients with advanced heart failure. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation.

Copyright © 2011. Published by Elsevier B.V.

PMID:
21536106
[PubMed - indexed for MEDLINE]
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