Differentiall loss of cytochrome-c oxidase subunits in ischemia-reperfusion iniurv:exacerbation of COI subunit loss by PKC-e inhibition

摘要

CO has 13 subunits and catalyzes the final enzymatic reactions in the electron transport chain (ETC) (59). It contributes significantly to maintenance of the mitochondrial electrochemical/proton gradient and the production of ATP (24) and is inhibited following prolonged I/R (55). Previously, Prabu et al. (51) reported impaired CO function following I/R injury in isolated rabbit hearts involving PKA-mediated phosphoryla-tion and degradation of CO I, IVi, and Vb subunits. However, there have been few cardiac studies exploring the regulation of CO following PC and even fewer exploring its regulation by individual PKC isozymes (16, 45, 47, 48). Our laboratory recently demonstrated that PKC-e coimmunoprecipitates with the number IV subunit of CO (COIV), which correlates with elevated CO activity during cardiac PC (16, 48). We hypothesize that there are multiple sites of PKC interaction with CO, and therefore, we determined which CO subunit levels were altered following PC, I/R, and PC ~+ I/R treatments.