S-nitrosylation: integrator of cardiovascular performance and oxygen delivery

Abstract

Delivery of oxygen to tissues is the primary function of the cardiovascular system. NO, a gasotransmitter that signals predominantly through protein S-nitrosylation to form S-nitrosothiols (SNOs) in target proteins, operates coordinately with oxygen in mammalian cellular systems. From this perspective, SNO-based signaling may have evolved as a major transducer of the cellular oxygen-sensing machinery that underlies global cardiovascular function. Here we review mechanisms that regulate S-nitrosylation in the context of its essential role in "systems-level" control of oxygen sensing, delivery, and utilization in the cardiovascular system, and we highlight examples of aberrant S-nitrosylation that may lead to altered oxygen homeostasis in cardiovascular diseases. Thus, through a bird's-eye view of S-nitrosylation in the cardiovascular system, we provide a conceptual framework that may be broadly applicable to the functioning of other cellular systems and physiological processes and that illuminates new therapeutic promise in cardiovascular medicine.

Nitric Oxide Regulates Skeletal Muscle Fatigue, Fiber Type, Microtubule Organization, and Mitochondrial ATP Synthesis Efficiency Through cGMP-Dependent Mechanisms

“…This contrasts with early studies suggesting that NO and cGMP promote skeletal muscle weakness (41,62). However, subsequent studies by the same group made the opposite conclusion that NO in fact promotes muscle contractility under physiological conditions (20,32). This reevaluation agrees with the majority of subsequent studies, including the present one, which provides new evidence that NO-cGMP signaling does not inhibit muscle strength (54,56).…”

Regulation of Cellular Communication by Signaling Microdomains in the Blood Vessel Wall

“…Since then, a number of intra-and intercellular targets for bioactive NO have been identified with the biological effects ranging from enzyme activation or inhibition, posttranslational modifications altering protein function, including S-nitrosylation and tyrosine nitrosation, and the generation of complex reactive nitrogen and oxygen species through the rapid spontaneous reaction of NO with other gaseous molecules in the cell (Ignarro, 1991;Davidge et al, 1995;Xu et al, 1998;Handy and Loscalzo, 2006;Yoshida et al, 2006;Kang-Decker et al, 2007;Selemidis et al, 2007;Zuckerbraun et al, 2007;Illi et al, 2008;Briones et al, 2009;Fernhoff et al, 2009;Lima et al, 2010;Thibeault et al, 2010;Bess et al, 2011;Choi et al, 2011;Straub et al, 2011;Marin et al, 2012;Haldar and Stamler, 2013;Korkmaz et al, 2013).…”

Hydrogen sulfide as an oxygen sensor

“…A number of mechanisms have been suggested, but none has achieved unequivocal support. Their pros and cons have been extensively reviewed (22,37,47,54,144,155,184,187). The intent of the present review is to examine the evidence suggesting that the O 2 -dependent metabolism of H 2 S is an O 2 sensor.…”