Protein S-nitrosylation in health and disease: a current perspective.
Protein S-nitrosylation constitutes a large part of the ubiquitous influence of nitric oxide on cellular signal transduction and accumulating evidence indicates important roles for S-nitrosylation both in normal physiology and in a broad spectrum of human diseases. Here we review recent findings that implicate S-nitrosylation in cardiovascular, pulmonary, musculoskeletal and neurological (dys)function, as well as in cancer. The emerging picture shows that, in many cases, pathophysiology correlates with hypo- or hyper-S-nitrosylation of specific protein targets rather than a general cellular insult due to loss of or enhanced nitric oxide synthase activity. In addition, it is increasingly evident that dysregulated S-nitrosylation can not only result from alterations in the expression, compartmentalization and/or activity of nitric oxide synthases, but can also reflect a contribution from denitrosylases, including prominently the S-nitrosoglutathione (GSNO)-metabolizing enzyme GSNO reductase. Finally, because exogenous mediators of protein S-nitrosylation or denitrosylation can substantially affect the development or progression of disease, potential therapeutic agents that modulate S-nitrosylation could well have broad clinical utility.
Foster
Matthew W
MW
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Hess
Douglas T
DT
Stamler
Jonathan S
JS
D000818:Animals; D004194:Disease / Q000209:etiology*; D006262:Health; D006801:Humans; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D015538:Nitrosation; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction
D009566:Nitrates; D011506:Proteins; D009569:Nitric Oxide