DIFFERENT ROLES OF PROTEIN-KINASE C-BETA AND C-DELTA IN ARACHIDONIC-ACID CASCADE, SUPEROXIDE FORMATION AND PHOSPHOINOSITIDE HYDROLYSIS

In contrast with protein kinase C (PKC)-beta, PKC-delta is exclusively detectable in the membrane fraction of liver macrophages. After long- term treatment with phorbol 12-myristate 13-acetate (PMA) PKC-beta is depleted faster (within 3 h) than PKC-delta (> 7 h). Simultaneously, p retreatment with PMA for 3 h inhibits the PMA- and zymosan-induced gen eration of superoxide and the PMA-induced formation of prostaglandin ( PG) E2, whereas a preincubation of more than 7 h is required to affect the zymosan-induced release of PGE2 and inositol phosphates. These re sults support an involvement of PKC-beta in the PMA-induced activation of the arachidonic acid cascade and in superoxide formation and imply an involvement of PKC-delta in zymosan-induced phosphoinositide hydro lysis and PGE2 formation. Two phorbol ester derivates, sapintoxin A (S APA) and 12-deoxyphorbol 13-phenylacetate 20-acetate (DOPPA), which ha ve been previously reported to activate preferentially PLC-beta but no t PKC-delta in vitro [Ryves, Evans, Olivier, Parker and Evans (1992) F EBS Lett. 288, 5-9], induce the formation of PGE2 and superoxide, down -regulate PKC-delta and potentiate inositol phosphate formation in par allel. SAPA, but not DOPPA, down-regulates PKC-beta and inhibits the P MA-induced formation of eicosanoids and superoxide.