S-nitrosylation in cardiovascular signaling.
Well over 2 decades have passed since the endothelium-derived relaxation factor was reported to be the gaseous molecule nitric oxide (NO). Although soluble guanylyl cyclase (which generates cyclic guanosine monophosphate, cGMP) was the first identified receptor for NO, it has become increasingly clear that NO exerts a ubiquitous influence in a cGMP-independent manner. In particular, many, if not most, effects of NO are mediated by S-nitrosylation, the covalent modification of a protein cysteine thiol by an NO group to generate an S-nitrosothiol (SNO). Moreover, within the current framework of NO biology, endothelium-derived relaxation factor activity (ie, G protein-coupled receptor-mediated, or shear-induced endothelium-derived NO bioactivity) is understood to involve a central role for SNOs, acting both as second messengers and signal effectors. Furthermore, essential roles for S-nitrosylation have been implicated in virtually all major functions of NO in the cardiovascular system. Here, we review the basic biochemistry of S-nitrosylation (and denitrosylation), discuss the role of S-nitrosylation in the vascular and cardiac functions of NO, and identify current and potential clinical applications.
Lima
Brian
B
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
Forrester
Michael T
MT
Hess
Douglas T
DT
Stamler
Jonathan S
JS
D000818:Animals; D017209:Apoptosis; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002319:Cardiovascular System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D026403:S-Nitrosothiols / Q000378:metabolism*; D015398:Signal Transduction; D014655:Vascular Resistance
D045462:Endothelium-Dependent Relaxing Factors; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D006152:Cyclic GMP