ACTIVATION OF PKC, SUPEROXIDE ANION PRODUCTION AND LDL LIPID-PEROXIDATION ARE NOT DEPENDENT ON PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE-C ACTIVITY IN U937 CELLS

Our previous studies have shown that both increase in Ca2+ levels and activation of protein kinase C (PKC) are required for monocyte-mediate d O-2(-) production and low density lipoprotein (LDL) peroxidation. Ph osphoinositide-specific phospholipase C (phosphoinositidase C or PIC) is believed to mediate release of intracellular Ca2+ through InsP(3) f ormation and activation of PKC through diacylglycerol (DAC). In these studies, we investigated the PIC pathway for its participation in mono cytic cell-mediated lipid peroxidation of LDL. We found substantial In sP, formation in opsonized zymosan (ZOP)-activated U937-b cells, indic ating the activation of PIC. Both inhibition of PIC by the PIC inhibit or U-73122 and reduction of the supply of the precursor lipid by lithi um chloride suppressed InsP, formation but did not alter LDL lipid per oxidation nor O-2(-) production by activated cells. Furthermore, we al so found that suppression of PIC activity had no substantial inhibitor y effect on PKC activity in ZOP-activated human monocytes. Our data su ggest that PIC activity is induced upon cell activation resulting in i ncreased levels of InsP(3). The activity of this pathway, however, is not required for cell-mediated O-2(-) production, PKC activation or LD L oxidation. (C) 1997 Elsevier Science B.V.