Abstract
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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alkaloids
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Animals
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Benzophenanthridines
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Body Weight / drug effects
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Creatine Kinase / metabolism
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Enzyme Activation / drug effects
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Enzyme Inhibitors / pharmacology
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Ethanol / pharmacology*
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Heart / drug effects*
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Heart / physiology
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Hemodynamics / drug effects
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In Vitro Techniques
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism*
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Male
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Mice
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Mice, Inbred C57BL
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Myocardial Contraction / drug effects
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Myocardial Contraction / physiology
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Myocardial Ischemia / metabolism
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Myocardial Reperfusion
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Myocardium / enzymology*
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Organ Size / drug effects
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Peptides / pharmacology
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Phenanthridines / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism*
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Protein Kinase C-epsilon
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Protein Serine-Threonine Kinases*
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Protein Transport / drug effects
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Recovery of Function / drug effects
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Reperfusion Injury / prevention & control
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Signal Transduction / drug effects
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Signal Transduction / physiology
Substances
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Alkaloids
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Benzophenanthridines
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Enzyme Inhibitors
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Isoenzymes
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Peptides
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Phenanthridines
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Proto-Oncogene Proteins
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Ethanol
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chelerythrine
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Prkce protein, mouse
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Protein Kinase C
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Protein Kinase C-epsilon
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Creatine Kinase