Possible contribution of protein kinase C activation to priming for DNA synthesis induced by epidermal growth factor with insulin and its inhibition by plasma membrane in primary cultured rat hepatocytes.
In primary cultured rat hepatocytes, DNA synthesis was markedly induced 48 h after plating by epidermal growth factor (EGF) and insulin added at 24 h, but not by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). When EGF and insulin were added at 6 h, DNA synthesis at 30 h was 7% of DNA synthesis seen at 48 h, but became 27% by pretreatment with TPA. The similar pretreatment effect was also seen with vasopressin. Such induction at 30 h was inhibited by rat liver plasma membrane added at 2 h even in the presence of TPA or vasopressin, and also by 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine more extensively than N-(2-guanidinoethyl)-5-isoquinolinesulfonamide. These results suggest that DNA synthesis induction by EGF and insulin may require a priming period related to protein kinase C activation in primary cultured rat hepatocytes, which is inhibited by plasma membrane.
Hirata
K
K
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Fujiwara
K
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects*; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007328:Insulin; D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; D014667:Vasopressins; D004815:Epidermal Growth Factor; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004247:DNA; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine