Protein kinase C translocation and PKC-dependent protein phosphorylation during myocardial ischemia

The present study demonstrates that the alpha, epsilon, and iota isozymes o f protein kinase C (PKC) are translocated to particulate fractions from the cytosol during brief intervals of global ischemia as well as reperfusion o f ischemic rat myocardium. In contrast, phorbol ester treatment of perfused hearts resulted in the translocation of the alpha, delta, and epsilon isoz ymes of PKC to particulate fractions. Additionally, the alpha, delta, and e psilon isozymes of PKC are translocated to particulate fractions in phorbol ester-stimulated, isolated adult rat cardiac myocytes. Concomitant with th e translocation of PKC isozymes to particulate fractions during myocardial ischemia, increased protein phosphorylation was observed, which was blocked by pretreatment of hearts with the selective PKC inhibitor bisindolylmalei mide I (50 nM). In particular, ischemia resulted in the phosphorylation of 26-, 20-, and 17-kDa particulate-associated proteins. Taken together, the p resent findings are the first to demonstrate that specific PKC isozymes are translocated to particulate fractions in the ischemic and the reperfused i schemic rat heart, resulting in the phosphorylation of specific particulate -associated proteins.