Bisindolylmaleimide inhibits the PMA-induced down-regulation of collagen synthesis in fibroblasts.
We assessed the role of protein kinase C (PKC) in the regulation of collagen synthesis. Two PKC activators, Phorbol 12-myristate 13-acetate (PMA) and 1-oleyl 2-acetyl-sn-glycerol (OAG), decreased the relative rate of collagen synthesis in a dose- and time-dependent manner in fibroblasts, whereas an inactive phorbol ester, 4 alpha-phorbol didecanoate failed to affect the collagen synthesis. In PKC-depleted cells both PMA and OAG were unable to inhibit collagen synthesis. Bisindolylmaleimide, a specific inhibitor of PKC, completely abrogated PMA-induced inhibition of collagen synthesis in a dose-dependent fashion while two other PKC inhibitors with low specificity, H7 and staurosporin failed to block PMA effect on collagen synthesis. The results provide evidence that collagen synthesis is regulated through the signal pathway involving PKC activation.
Park
R W
RW
Department of Biochemistry, School of Medicine, Kyungpook National University, Taegu, Korea.
Kim
I S
IS
Jo
J S
JS
D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D003513:Cycloheximide / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008301:Maleimides / Q000494:pharmacology*; D011347:Procollagen / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004075:Diglycerides; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D011347:Procollagen; D012333:RNA, Messenger; C038237:1-oleoyl-2-acetylglycerol; D003094:Collagen; D003513:Cycloheximide; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D011493:Protein Kinase C; C088060:bisindolylmaleimide; D013755:Tetradecanoylphorbol Acetate