therapeuticpotentialofagentsthataffectS-nitrosylationis through altered expression or activity of enzymes that
being explored with promising results (Table 2). These control the availability of endogenous NOS substrates
agentshavethepotentialtorestoredeficientSNO-proteins (e.g.L-Arg)orendogenousNOSinhibitors(e.g.asymmetric
to physiological levels or to otherwise influence cellular dimethylarginine, ADMA). In addition, a number of
signaling pathways that are mediated or modulated by enzymes in the L-Arg/NO pathway are also targets of
S-nitrosylation. For example, SNO-repleting agents are regulatory S-nitrosylation [1], including arginase, which
highly efficacious in the setting of inflammation, including catabolizes L-Arg. Arginase 1 (Arg1; cytosolic arginase) is
experimental models of lung injury, stroke and multiple activated through enhanced multimerization resulting
sclerosis,inwhichS-nitrosylationseemstoplayamajorrole from S-nitrosylation at cysteine 303 (C303) [13]. Arg1
in expression of the innate immune response [9–12].This S-nitrosylation and activation coincide with increased
review focuses on the numerous proteins and signaling iNOS expression in the aortic endothelium of aging rats
pathways that are regulated by S-nitrosylation in the con- [13]andcancontributetoage-relatedendothelialdysfunc-
text of diseases, in which aberrant S-nitrosylation has tion and vascular stiffness [14]. Levels of the bronchodi-
recently been implicated. lator GSNO are low in asthmatic airways [2] and a causal
link between SNO depletion and arginase levels has been
Modulation of SNO production: NO synthases and suggested [15]: Arg1 and Arg2 are upregulated in human
organic nitrates asthma and in experimental asthma models [16,17] and
Intissuesandextracellularfluids,SNOlevelsarelikelyto singlenucleotidepolymorphisms(SNPs)ingenesencoding
reflect NOS activity and, accordingly, can be modulated Arg1 and Arg2 are associated with increased risk of
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