major sources of endogenous NO, and stimulus-coupled of NOS enzymes with target proteins, including direct本文来自辣.文,论-文·网原文请找腾讯324.9114
activation or induction of NO synthases has been shown interactions,seemsinmanycasestobeanimportantdeter-
to mediate or modulate a broad range of cellular signaling minant of S-nitrosylation under physiological conditions;
pathways. The physiological influence of NO is exerted accordingly,aberrantNOSlocalizationseemstobeinvolved
predominantly through the posttranslational modification inatleastseveraldiseases(Figure1).Suchdeficitscanhave
andfunctionalregulationofproteins.Itwasfirstestablished a genetic basis. For example, in a variant of long QT
that nitrosylation of heme iron within soluble guanylate syndrome, a mutation in an nNOS scaffold protein results
cyclase activates the enzyme to generate cyclic GMP and in disinhibition of nNOS and aberrant S-nitrosylation of a
therebysubservesNO-basedvasoactivity.However,hemes cardiac ion channel [5]. In addition to localization, it has
donotgenerallyelicitcellularsignalinginvolvingposttran- been established that transfer of NO groups between
slational modification of proteins and thus an explanation proteins and glutathione governs a cellular equilibrium
for most NO-based bioactivity was not apparent. Sub- between low-molecular-weight and protein S-nitrosothiols
sequently,alargebodyofexperimentalevidencehasdemon- (SNOs) (Figure 2). In mouse models, genetic ablation of
strated that S-nitrosylation of Cys residues within a broad S-nitrosoglutathione reductase (GSNOR), the enzyme
functionalspectrumofproteinsconstitutealargepartofthe principally responsible for GSNO metabolism, results in
ubiquitous influence of NO on cellular function [1]. enhanced levels of SNO-proteins and significantly attenu-
ates
hindi sms http://www.hindisms-hindi.com/ experimental asthma and heart failure [6,7],but
Corresponding author: Stamler, J.S. (increases the severity of endotoxic shock [8]. Finally, the
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