Nuclear translocation of PKC zeta during ischemia and its inhibition by wortmannin, an inhibitor of phosphatidylinositol 3-kinase.

Protein kinase C zeta (PKC zeta), a member of the atypical PKC subgroup, is insensitive to Ca2+, diacylglycerol, and phorbol esters, but is activated by phospholipids such as phosphatidylinositol-3,4,5-triphosphate, a product of phosphatidylinositol 3-kinase (PI3-kinase). Here we show that PKC zeta translocates from the cytosol to the 1000 x g pellet (nuclear-myofibrillar) fraction during ischemia for 40 min in Langendorff-perfused rat hearts. In addition, immunohistochemical observation shows that ischemia induces the translocation of PKC zeta to the nucleus. The nuclear translocation during ischemia is inhibited in a dose-dependent manner by wortmannin (10(-9)-10(-7) M), an inhibitor of PI3-kinase.