Moderate alcohol consumption induces sustained cardiac protection by activating PKC-epsilon and Akt.
C57BL/6 mice were fed 18% ethanol (vol/vol) in drinking water for 12 wk. Isovolumic hearts were subjected to 20 min of ischemia and 30 min of reperfusion on a Langendorff apparatus. There were no differences in baseline hemodynamic function between hearts from ethanol (EtOH)-fed mice and controls. However, prior alcohol consumption doubled recovery of left ventricular developed pressure (68 +/- 8 vs. 33 +/- 8 mmHg for controls; n = 10, P < 0.05) and reduced creatine kinase release by half (0.26 +/- 0.04 vs. 0.51 +/- 0.08 U x min(-1) x g wet wt(-1) for controls; n = 10, P < 0.05). EtOH feeding doubled expression of activated protein kinase C epsilon (PKC)epsilon (n = 6, P < 0.05); whereas PKC inhibition blocked protection during ischemia-reperfusion. EtOH feeding also increased expression of Akt three- to fivefold (n = 6, P < 0.05), whereas PKC inhibition prevented increases in Akt kinase activity. We conclude that signaling pathways involving PKC-epsilon are critical for sustained EtOH-mediated cardioprotection and that Akt may be a downstream effector of resistance to myocardial reperfusion injury.
Zhou
Hui-Zhong
HZ
Cardiology Section, San Francisco Veterans Affairs Medical Center and Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA.
Karliner
Joel S
JS
Gray
Mary O
MO
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D001835:Body Weight / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology*; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051744:Protein Kinase C-epsilon; D017346:Protein Serine-Threonine Kinases; D021381:Protein Transport / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D020127:Recovery of Function / Q000187:drug effects; D015427:Reperfusion Injury / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010455:Peptides; D010617:Phenanthridines; D011518:Proto-Oncogene Proteins; D000431:Ethanol; C016299:chelerythrine; C497256:Prkce protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D003402:Creatine Kinase