Protein kinase C and cell proliferation in spontaneously hypertensive rats.
Cultured aortic fibroblasts from spontaneously hypertensive rats (SHR) exhibit increased proliferation rate compared with cells from normotensive Wistar Kyoto (WKY) rats. The present study was designed to investigate whether this growth abnormality could be accounted for by alteration in protein kinase C (PKC). The enzyme activation by 12-O-tetradecanoyl phorbol 13-acetate (TPA) promoted 3H-thymidine incorporation which was higher in SHR-derived fibroblasts compared with WKY-derived cells. Likewise, 3H-phorbol 12,13-dibutyrate (PDBu) binding to intact cells was markedly increased in SHR-derived fibroblasts. These findings suggest a difference in PKC activity between the two cell types. In both cell types, serum-induced 3H-thymidine incorporation was enhanced by PKC down-regulation, which was obtained by prolonged treatment of cells with high dose of TPA, whereas it was inhibited in a dose-dependent manner by activation of the enzyme. The changes in serum-induced 3H-thymidine incorporation elicited either by activation or desensitization of PKC, did not differ between SHR and WKY fibroblasts. Our results indicate therefore i) that in the presence of serum PKC exerts an antiproliferative effect in rat aortic fibroblasts and ii) that the increase in PKC activity and in sensitivity to TPA exhibited by SHR-derived fibroblasts, is not involved in the increased proliferation rate displayed by SHR-derived fibroblasts in serum-containing medium.
Zhu
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DL
Service de Biochimie de la Faculté de Médecine Paris-Ouest Université René Descartes, Paris, France.
Herembert
T
T
Marche
P
P
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000493:pharmacokinetics
D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine