Arachidonic acid-induced down-regulation of protein kinase C δ in beta- cells

We have previously identified expression of multiple protein kinase C (PKC) isoforms in insulinoma-derived beta-cells and whole islets. Both PKC δ and PKC α appear to be the more abundantly expressed isoforms. In this report we studied the effects of arachidonic acid (AA) on the subcellular distribution of PKC α and PKC δ. AA has been reported to activate both PKC α and PKC δ and it is thought to be an important second messenger in beta- cells. Here we report that M interacted with and altered beta-cell pools of PKC δ preferentially over PKC α. AA (100 μM) over the course of 45 min reduced cytosolic levels of PKC δ (to 40 ± 15%, compared to time zero control) leaving membrane- and cytoskeleton-associated levels near control levels. Analysis of whole cell homogenates showed a slight down-regulation of PKC δ indicating proteolysis. The down-regulation of cytosolic PKC δ appeared to be isoform specific since cytosolic PKC α remained at control levels over the time course. The response was dose-dependent and negligible at concentrations below 30 μM and occurred, at least partially, in the cytosolic compartment of the cell. Indomethacin also down-regulated cytosolic PKC δ preferentially over PKC α possibly through accumulation of AA. These findings suggest that cytosolic PKC δ may be a downstream target of this beta-cell second messenger.