Expression of activated PKC epsilon (PKCε) protects the ischemic heart, without attenuating ischemic H+ production

H. R. CROSS, E. MURPHY, R. BOLLI, P. PING AND C. STEENBERGEN. Expression of Activated PKC Epsilon (PKCepsilon) Protects the Ischemic Heart, without Attenuating Ischemic H Production. Journal of Molecular and Cellular Cardiology (2002) 34, 361-367. PKCepsilon is a PKC isoform that translocates during preconditioning and may mediate cardioprotection. To investigate whether PM activation is cardioprotective, Langendorff-perfused hearts from wild-type (WT) mice and from mice expressing constitutively active mutant PKCe were subjected to 20min ischemia and 40 min reperfusion while P-31 NMR spectra were acquired. Pre-ischemic glycogen levels were similar in WT and PKCs hearts. During ischemia, ATP fell less in PKCs than in WT hearts. Ischemic intracellular pH, however, was similar in WT and PKCepsilon hearts. During reperfusion, recovery of contractile function and ATP were greater in PKCe than WT hearts. In conclusion, expression of activated PKCe protected hearts from post-ischemic energetic and contractile dysfunction, consistent with the proposed cardioprotective role of PKCepsilon. Protection occurred in the PKCe hearts without attenuation of ischemic H+ production, implying that, at least in this ischemic model, reduced acidification during ischemia is not necessary for cardioprotection. (C) 2002 Elsevier Science Ltd. All rights reserved.