Calphostin C induces expression of amphiregulin mRNA via reactive oxygen species in IEC-6 cells.
Calphostin C, a secondary metabolite of the fungus Cladosporium cladosporioides, is generally used as a specific inhibitor of protein kinase C. It is known that 12-O-tetradecanoyl-13-phorbol acetate (TPA), a protein kinase C activator, induces expression of mRNA for amphiregulin (AR), a member of EGF-related polypeptides, in mammalian epithelial cells. 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 expression of AR mRNA. Moreover, calphostin C alone induced expression of AR mRNA in a light-dependent manner, and this effect was abrogated by pretreatment with N-acetylcysteine. These results suggest that calphostin C can upregulate expression of AR mRNA via reactive oxygen species.
Miyazaki
Y
Y
Second Department of Internal Medicine, Osaka University Medical School, Suita, Japan. miyazaki@imed2.med.osaka-u.ac.jp
Shinomura
Y
Y
Tsutsui
S
S
Kitamura
S
S
Hiraoka
S
S
Matsuzawa
Y
Y
D000111:Acetylcysteine / Q000494:pharmacology; D066258:Amphiregulin; D000818:Animals; D002460:Cell Line; D004347:Drug Interactions; D066255:EGF Family of Proteins; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006023:Glycoproteins / Q000096:biosynthesis*; D006133:Growth Substances / Q000096:biosynthesis*; D036341:Intercellular Signaling Peptides and Proteins; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D009281:Naphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D066258:Amphiregulin; C587850:Areg protein, rat; D066255:EGF Family of Proteins; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D006023:Glycoproteins; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D009281:Naphthalenes; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate; D000111:Acetylcysteine