A possible mechanism of TPA-mediated downregulation of neurotrophin-3 geneexpression in rat cultured vascular smooth muscle cells

We have previously reported that in cultured rat vascular smooth muscle cel ls (VSMCs), neurotrophin-3 (NT-3) gene expression was suppressed by TPA (12 -O-tetradecanoyl phorbol-13-acetate), which induces an AP-1 transcription f actor. In the present study, to clarify the mechanism for TPA-mediated down regulation of NT-3 gene expression, effects of cycloheximide and dexamethas one (Dex) on the TPA-mediated downregulation were examined in VSMCs. Pretre atment with cycloheximide, an inhibitor of protein synthesis, or simultaneo us treatment with Dex, an inhibitor of AP-1, suppressed the TPA-mediated do wnregulation of NT-3 gene expression. Furthermore, co-transfection of c-fos and c-jun expression vectors into VSMCs resulted in decrease in the NT-3 g ene expression. The present findings suggest that TPA-induced AP-1 de novo synthesis causes the downregulation of NT-3 gene expression in VSMCs. (C) 1 999 Elsevier Science B.V. All rights reserved.