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

AbstractProtein kinase Cζ (PKCζ), 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 PKCζ translocates from the cytosol to the 1000×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 PKCζ 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