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We investigated the effect of two GSH (glutathione) precursors, NAC (<jats:italic>N<\/jats:italic>\u2010acetylcysteine) and cystine as the physiological carrier of cysteine in GSH with added selenomethionine (F1) in preventing spermine (uraemic toxin)\u2010induced apoptosis in cultured human aortic VSMC (vascular smooth muscle cells). VSMCs exposed to spermine (15 \u03bcM) with or without antioxidants (doses 50, 100, 200 and 500 \u03bcg\/ml) were assessed for apoptosis, JNK (c\u2010Jun\u2010NH<jats:sub>2<\/jats:sub>\u2010terminal kinase) activation and iNOS (inducible nitric oxide synthase) induction and activation of intrinsic pathway signalling. Spermine exposure resulted in activation of JNK and iNOS induction and apoptosis. NAC and F1 (dose range 50\u2013500 \u03bcg\/ml) attenuated spermine\u2010induced acceleration of VSMC apoptosis but only F1 (at 200 and 500 \u03bcg\/ml) maintained spermine\u2010induced apoptosis at control levels. Spermine\u2010induced JNK activation was prevented by 200 \u03bcg\/ml of both NAC and F1, while iNOS induction was blocked only by F1. Notably, the adverse effects of spermine on BAX\/BCL\u20102 ratio, cytochrome <jats:italic>c<\/jats:italic> release and caspase activation was fully attenuated by F1. In conclusion, F1 was more effective than NAC in preventing spermine\u2010induced apoptosis and downstream changes in related signal transduction pathways in VSMCs. Further studies are needed to examine the effect of these compounds in preventing CKD\u2010associated vascular disease.<\/jats:p>","DOI":"10.1042\/cbi20090349","type":"journal-article","created":{"date-parts":[[2010,2,3]],"date-time":"2010-02-03T12:56:21Z","timestamp":1265201781000},"page":"503-511","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Inhibition of apoptotic signalling in spermine\u2010treated vascular smooth muscle cells by a novel glutathione 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