Independent inhibition of DNA synthesis by protein kinase C, cyclic AMP and interferon alpha/beta in rabbit aortic smooth muscle cells.
In quiescent cultures of rabbit aortic smooth muscle cells, whole blood serum-induced DNA synthesis was inhibited markedly by protein kinase C-activating 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and phorbol-12, 13-dibutyrate (PDBu), cyclic AMP-derivatives, such as dibutyryl cyclic AMP (Bt2cAMP) and 8-bromo-cyclic AMP, and interferon alpha/beta. Neither TPA nor interferon alpha/beta elevated the cellular cyclic AMP level. Neither Bt2cAMP nor interferon alpha/beta induced the phospholipase C-mediated hydrolysis of phosphoinositides. The down-regulation of protein kinase C by prolonged treatment with PDBu abolished the antiproliferative action of TPA but did not affect that of Bt2cAMP or interferon alpha/beta. TPA and Bt2cAMP inhibited the serum-induced DNA synthesis when added within 12 h after the addition of the serum, while interferon alpha/beta was active only when added within 6 h. These results suggest that there are at least three independent signaling systems, protein kinase C- and cyclic AMP-mediated systems and an unidentified system for interferon alpha/beta, which are involved in the antiproliferative mechanisms in rabbit aortic smooth muscle cells.
Fukumoto
Y
Y
Department of Biochemistry, Kobe University School of Medicine, Japan.
Kawahara
Y
Y
Kariya
K
K
Araki
S
S
Fukuzaki
H
H
Takai
Y
Y
D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D007295:Inositol Phosphates / Q000378:metabolism; D007370:Interferon Type I / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011493:Protein Kinase C / Q000502:physiology*; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007295:Inositol Phosphates; D007370:Interferon Type I; D004247:DNA; D000242:Cyclic AMP; D011493:Protein Kinase C; D000527:Alprostadil; D013755:Tetradecanoylphorbol Acetate