PKC delta is required for mitochondrial-dependent apoptosis in salivary epithelial cells

We report here that the novel protein kinase C isoform, PKC delta, is requi red at or prior to the level of the mitochondria for apoptosis induced by a diverse group of cell toxins. We have used adenoviral expression of a kina se-dead (KD) mutant of PKC delta to explore the requirement for PKC delta i n the mitochondrial-dependent apoptotic pathway. Expression of PKC delta KD , but not PKC delta KD, in salivary epithelial cells resulted in a dose-dep endent inhibition of apoptosis induced by etoposide, UV-irradiation, brefel din A, and paclitaxel. DNA fragmentation was blocked up to 71% in parotid C 5 cells infected with the PKC delta KD adenovirus, whereas caspase-3 activi ty was inhibited up to 65%. The activation of caspase-9-like proteases by a ll agents was also inhibited in parotid C5 cells expressing PKC delta KD. T he ability of PKC delta KD to block the loss of mitochondrial membrane pote ntial was similarly determined. Expression of PKC delta KD blocked the decr ease in mitochondrial membrane potential observed in cells treated with eto poside, UV, brefeldin A, or paclitaxel in a dose-dependent manner. In contr ast to the protective function of PKC delta KD, expression of PKC delta WT resulted in a potent induction of apoptosis, which could be inhibited by co infection with PKC delta KD. These results suggest that PKC delta is a comm on intermediate in mitochondrial-dependent apoptosis in salivary epithelial cells.