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2012 ; 1820
(6
): 752-62
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Regulation of cardiovascular cellular processes by S-nitrosylation
#MMPMID21536106
Schulman IH
; Hare JM
Biochim Biophys Acta
2012[Jun]; 1820
(6
): 752-62
PMID21536106
show ga
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.
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