Protein S-nitrosylation in health and disease: a current perspectiveProtein S-nitrosylation constitutes a large part of the ExpressionofiNOSisinducedinmanymammaliancell
ubiquitous influence of nitric oxide on cellular signal types by a variety of stressors or injury and the cytotoxic
transduction and accumulating evidence indicates action of NO, generated in particular by phagocytic cells,
important roles for S-nitrosylation both in normal raised the possibility that NO generated at relatively high
physiologyandinabroadspectrumofhumandiseases. and sustained levels by iNOS could compromise cellular
Here we review recent findings that implicate S-nitro- function through generalized nitrosative stress. However,
sylation in cardiovascular, pulmonary, musculoskeletal the emerging recognition that NO is involved in a multi-
andneurological(dys)function,aswellasincancer.The plicity of cellular signal transduction pathways throughhindi sms http://www.hindisms-hindi.com/
emergingpictureshowsthat,inmanycases,pathophy- protein S-nitrosylation pointed to the possibility that dys-
siologycorrelateswithhypo-orhyper-S-nitrosylat本文来自辣.文,论-文·网原文请找腾讯3249.114 ionof regulatedS-nitrosylationcouldcontributetopathophysiol-
specific protein targets rather than a general cellular ogies characteristic of a wide range of disease states [2].
insult due to loss of or enhanced nitric oxide synthase Therelativelyrecentdevelopmentofimprovedmethodsfor
activity. In addition, it is increasingly evident that analysis of protein S-nitrosylation [3,4] has facilitated the
dysregulated S-nitrosylation can not only result from identification of numerous S-nitrosylated proteins (SNO-
alterations in the expression, compartmentalization proteins) for which levels of S-nitrosylation can be altered
and/or activity of nitric oxide synthases, but can also in disease. The emerging picture shows that hypo- or
reflect a contribution from denitrosylases, including hyper-S-nitrosylation of these specific protein targets
prominently the S-nitrosoglutathione (GSNO)-metabo- (whichresultinalterationsinproteinfunction)aredirectly
lizing enzyme GSNO reductase. Finally, because implicated in the etiology and symptomatology of an
exogenousmediatorsofproteinS-nitrosylationordeni- increasing number of human diseases, prominently in-
trosylation can substantially affect the development or cluding disorders of the cardiovascular, musculoskeletal
progression of disease, potential therapeutic agents and nervous systems (Table 1). In a number of cases,
that modulate S-nitrosylation could well have broad specific Cys residues that are the loci of (patho)physiolo-
clinical utility. gical regulation by S-nitrosylation have been identified.
Themolecularmechanismsunderlying(dys)regulationof
Introduction S-nitrosylation and possible approaches to therapeutic
Inmammaliancells,theL-Arg-dependentnitricoxide(NO) alteration of SNO-protein levels are now the focus of
synthases – neuronal NOS (nNOS, NOS1), inducible NOS increasingattention.AlthoughNOSexpressionandactivity
(iNOS,NOS2)andendothelialNOS(eNOS,NOS3)–arethe areobviousgovernorsofS-nitrosylation,theco-localization2494