POSSIBLE ROLE OF NA-INDUCED DOWN-REGULATION OF PROTEIN-KINASE-C IN HL-60 CELLS( INFLUX IN PHORBOL ESTER)

Amiloride, an inhibitor of Na+/H+ exchange, inhibited down-regulation of protein kinase C in HL60 cells induced by tumor-promoting phorbol e ster in dose-dependent manner judging from immunoblot analysis. This i nhibition 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 Na-22+ uptake by H L60 cells, the higher uptake was observed after stimulation with phorb ol ester compared to the control cells and this Na-22+ uptake was stro ngly inhibited by the addition of amiloride. However, monensin further stimulated the Na-22+ uptake observed in phorbol ester-treated cells. These data suggest that the increase in intracellular Na+ concentrati on may be one of the triggers for the induction of down regulation of protein kinase C.