title: Possible role of Na+ influx in phorbol ester-induced down-regulation of protein kinase C in HL60 cells.
abstract: Amiloride, an inhibitor of Na+/H+ exchange, inhibited down-regulation of protein kinase C in HL60 cells induced by tumor-promoting phorbol ester in dose-dependent manner judging from immunoblot analysis. This inhibition was observed with regard to type I (gamma), type II (beta), and type III (alpha) isozymes of protein kinase C. On the other hand, monensin, a Na+ ionophore, accelerated the down-regulation of protein kinase C induced by phorbol ester. When we examined 22Na+ uptake by HL60 cells, the higher uptake was observed after stimulation with phorbol ester compared to the control cells and this 22Na+ uptake was strongly inhibited by the addition of amiloride. However, monensin further stimulated the 22Na+ uptake observed in phorbol ester-treated cells. These data suggest that the increase in intracellular Na+ concentration may be one of the triggers for the induction of down regulation of protein kinase C.
authors.affiliation: Department of Internal Medicine, Fukui Medical School, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Takeuchi
authors.forename: E
authors.initials: E
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: F
authors.initials: F
authors.lastname: Takeuchi
authors.forename: K
authors.initials: K
authors.lastname: Sada
authors.forename: H
authors.initials: H
authors.lastname: Yamamura
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D001692:Biological Transport; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D008985:Monensin / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000584:Amiloride; D008985:Monensin; D012964:Sodium; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate