INDUCTION OF APOPTOSIS BY PYRROLIDINEDITHIOCARBAMATE AND N-ACETYLCYSTEINE IN VASCULAR SMOOTH-MUSCLE CELLS

Pyrrolidinedithiocarbamate (PDTC) and N-acetylcysteine (NAG) have been used as antioxidants to prevent apoptosis in lymphocytes, neurons, an d vascular endothelial cells, We report here that PDTC and NAC induce apoptosis in rat and human smooth muscle cells, In rat aortic smooth m uscle cells, PDTC induced cell shrinkage, chromatin condensation, and DNA strand breaks consistent with apoptosis. In addition, overexpressi on of Bcl-2 suppressed vascular smooth muscle cell death caused by PDT C and NAG. The viability of rat aortic smooth muscle cells decreased w ithin 3 h of treatment with PDTC and was reduced to 30% at 12 h. The e ffect of PDTC and NAC on smooth muscle cells was not species specific because PDTC and NAC both caused dose-dependent reductions in viabilit y in rat and human aortic smooth muscle cells. In contrast, neither PD TC nor NAC reduced viability in human aortic endothelial cells. The us e of antioxidants to induce apoptosis in vascular smooth muscle cells may help prevent their proliferation in arteriosclerotic lesions.