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 subgrou p, is insensitive to Ca2+, diacylglycerol, and phorbol esters, but is activated by phospholipids such as phosphatidylinositol-3,4,5-triphosp hate, a product of phosphatidylinositol 3-kinase (PI3-kinase). Here we show that PKC zeta translocates from the cytosol to the 1000 X g pell et (nuclear-myofibrillar) fraction during ischemia for 40 min in Lange ndorff-perfused rat hearts. In addition, immunohistochemical observati on shows that ischemia induces the translocation of PKC zeta to the nu cleus. The nuclear translocation during ischemia is inhibited in a dos e-dependent manner by wortmannin (10(-9)-10(-7) M), an inhibitor of PI 3-kinase.