CALPHOSTIN-C INDUCES EXPRESSION OF AMPHIREGULIN MESSENGER-RNA VIA REACTIVE OXYGEN SPECIES IN IEC-6 CELLS

Calphostin C, a secondary metabolite of the fungus Cladosporium clados porioides, is generally used as a specific inhibitor of protein kinase C. It is known that 12-O-tetradecanoyl-13-phorbol acetate (TPA), a pr otein kinase C activator, induces expression of mRNA for amphiregulin (AR), a member of EGF-related polypeptides, in mammalian epithelial ce lls. In this work, we determined the effect of calphostin C on AR mRNA expression in IEC-6 cells, a rat intestinal epithelial cell line, and unexpectedly found that this compound enhanced the TPA-induced expres sion of AR mRNA. Moreover, calphostin C alone induced expression of AR mRNA in a light-dependent manner, and this effect was abrogated by pr etreatment with N-acetylcysteine. These results suggest that calphosti n C can upregulate expression of AR mRNA via reactive oxygen species. (C) 1998 Elsevier Science Inc.