Oxidation and nitrosation of thiols at low micromolar exposure to nitric oxide. Evidence for a free radical mechanism

Jourd'heuil, David, Jourd'heuil, Frances L. and Feelisch, Martin (2003) Oxidation and nitrosation of thiols at low micromolar exposure to nitric oxide. Evidence for a free radical mechanism The Journal of Biological Chemistry, 278, (18), pp. 15720-15726. (doi:10.1074/jbc.M300203200). (PMID:12595536).


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Although the nitric oxide (.NO)-mediated nitrosation of thiol-containing molecules is increasingly recognized as an important post-translational modification in cell signaling and pathology, little is known about the factors that govern this process in vivo. In the present study, we examined the chemical pathways of nitrosothiol (RSNO) production at low micromolar concentrations of .NO. Our results indicate that, in addition to nitrosation by the .NO derivative dinitrogen trioxide (N2O3), RSNOs may be formed via intermediate one-electron oxidation of thiols, possibly mediated by nitrogen dioxide (.NO2), and the subsequent reaction of thiyl radicals with .NO. In vitro, the formation of S-nitrosoglutathione (GSNO) from .NO and excess glutathione (GSH) was accompanied by the formation of glutathione disulfide, which could not be ascribed to the secondary reaction of GSH with GSNO. Superoxide dismutase significantly increased GSNO yields and the thiyl radical trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO), inhibited by 45 and 98% the formation of GSNO and GSSG, respectively. Maximum nitrosation yields were obtained at an oxygen concentration of 3%, whereas higher oxygen tensions decreased GSNO and increased GSSG formation. When murine fibroblasts were exposed to exogenous .NO, RSNO formation was sensitive to DMPO and oxygen tension in a manner similar to that observed with GSH alone. Our data indicate that RSNO formation is favored at oxygen concentrations that typically occur in tissues. Nitrosothiol formation in vivo depends not only on the availability of .NO and O2 but also on the degree of oxidative stress by affecting the steady-state concentration of thiyl radicals.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1074/jbc.M300203200
ISSNs: 0021-9258 (print)
Keywords: 3T3 cells, free radicals, nitric oxide, glutathione disulfide, s-nitrosoglutathione
Organisations: Clinical & Experimental Sciences
ePrint ID: 337857
Date :
Date Event
2 May 2003Published
Date Deposited: 22 Jun 2012 11:18
Last Modified: 17 Apr 2017 17:13
Further Information:Google Scholar
URI: http://eprints.soton.ac.uk/id/eprint/337857

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