Antiproliferative action of protein kinase C in cultured rabbit aortic smooth muscle cells.
In rabbit aortic smooth muscle cells (SMC), protein kinase C-activating 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibited the whole blood serum (WBS)-induced DNA synthesis. The inhibitory action of TPA was mimicked by another protein kinase C-activating phorbol ester, phorbol-12,13-dibutyrate (PDBu), but not by 4 alpha-phorbol-12,13- didecanoate known to be inactive for this enzyme. Prolonged treatment of the cells with PDBu caused the down-regulation of protein kinase C. In these cells, WBS still induced DNA synthesis but the inhibitory action of TPA was abolished. DNA synthesis started at 18 h and reached a maximal level 24 h after the addition of WBS. TPA inhibited the WBS-induced DNA synthesis even when added 12 h after the addition of WBS. These results suggest that protein kinase C has an antiproliferative action in rabbit aortic SMC and that this action is attributed to the inhibition of the progression from the late G1 into S phase of the cell cycle. TPA also inhibited the phospholipase C-mediated hydrolysis of phosphoinositides which was induced by WBS within several minutes, but the relevance of this effect on the antiproliferative action of TPA is uncertain.
Kariya
K
K
Department of Internal Medicine, Kobe University School of Medicine, Japan.
Fukumoto
Y
Y
Tsuda
T
T
Yamamoto
T
T
Kawahara
Y
Y
Fukuzaki
H
H
Takai
Y
Y
D000818:Animals; D001013:Aorta, Thoracic; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D006868:Hydrolysis; D007399:Interphase / Q000187:drug effects; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010716:Phosphatidylinositols / Q000097:blood; D011493:Protein Kinase C / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology
D010716:Phosphatidylinositols; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate