Independent inhibition of DNA synthesis by protein kinase C, cyclic AMP and interferon α/β in rabbit aortic smooth muscle cells

Autor: Yoshimi Takai, Hisashi Fukuzaki, Yasuo Fukumoto, Yasuhiro Kawahara, Ken-ichi Kariya, Shun-ichi Araki
Rok vydání: 1988
Předmět:
Zdroj: Biochemical and Biophysical Research Communications. 157:337-345
ISSN: 0006-291X
DOI: 10.1016/s0006-291x(88)80052-4
Popis: 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.
Databáze: OpenAIRE