Abstract 17041: Attenuating the Interaction Between Delta PKC (dPKC) and the d Subunit of F1Fo ATP Synthase (dF1Fo) protects Against Myocardial Infarction in Rats

Our laboratory previously, developed a mitochondrially-targeted peptide inhibitor [NH2-YGRKKRRQRRRMLATRALSLIGKRAISTSVC-COOH] of the dPKC-dF1Fo interaction that improves contractility and energetics, and reduces infarction following ischemia / reperfusion (IR) injury in perfused rat hearts. In the present study we tested the hypothesis that dPKC inhibits ATP production in vivo via an interaction with dF1Fo to exacerbate cardiac IR injury. In rats administered the dPKC-dF1Fo inhibitor (5 ug/kg) intravenously (I.V.) for 20 min, we observed substantial FLAG immunoreactivity (The dPKC-dF1Fo inhibitor is tagged with a FLAG epitope) in cardiac subsarcolemmal (SSM) and interfibrillar (IFM) mitochondria (n=6, p<0.03 and p<0.006). In rats receiving a 10 min coronary occlusion we observed a 5-fold induction of dPKC-dF1Fo co-immunoprecipitation (co-IP) in the left ventricular (LV) region at risk (RAR) for ischemia). This was reduced by 71 +/- 13 %,( p<0.001, n=8) in rats receiving the dPKC-dF1Fo inhibitor I.V. In add...