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Cardioprotection from Ischemia by a Brief Exposure to Physiological Levels of Ethanol: Role of Epsilon Protein Kinase C

Chen, Che-Hong ; Gray, Mary O. ; Mochly-Rosen, Daria

Proceedings of the National Academy of Sciences - PNAS, 1999-10, Vol.96 (22), p.12784-12789 [Periódico revisado por pares]

United States: National Academy of Sciences of the United States of America

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Título:
Cardioprotection from Ischemia by a Brief Exposure to Physiological Levels of Ethanol: Role of Epsilon Protein Kinase C
Autor: Chen, Che-Hong ; Gray, Mary O. ; Mochly-Rosen, Daria
Assuntos: Adhesins, Bacterial ; Alcohol drinking ; Amino Acid Sequence ; Animals ; Biological Sciences ; Blotting, Western ; Cardiovascular agents ; Cardiovascular disease ; Carrier Proteins - chemistry ; Carrier Proteins - genetics ; Carrier Proteins - immunology ; Dose-Response Relationship, Drug ; Enzyme Inhibitors - therapeutic use ; Enzymes ; Epidemiology ; Ethanol ; Ethanol - therapeutic use ; Heart ; In Vitro Techniques ; Insults ; Ischemia ; Isoenzymes - antagonists & inhibitors ; Isoenzymes - metabolism ; Male ; Molecular Sequence Data ; Myocardial Ischemia - enzymology ; Myocardial Ischemia - prevention & control ; Myocardium ; Osmotic fragility ; Particulate matter ; Preconditioning ; Protein Kinase C - antagonists & inhibitors ; Protein Kinase C - metabolism ; Protein Kinase C-epsilon ; Rats ; Rats, Wistar ; Reperfusion Injury - prevention & control
É parte de: Proceedings of the National Academy of Sciences - PNAS, 1999-10, Vol.96 (22), p.12784-12789
Notas: Edited by David M. Kipnis, Washington University School of Medicine, St. Louis, MO, and approved August 24, 1999
To whom reprint requests should be addressed. E-mail: mochly@stanford.edu.
Descrição: Recent epidemiological studies indicate beneficial effects of moderate ethanol consumption in ischemic heart disease. Most studies, however, focus on the effect of long-term consumption of ethanol. In this study, we determined whether brief exposure to ethanol immediately before ischemia also produces cardioprotection. In addition, because protein kinase C (PKC) has been shown to mediate protection of the heart from ischemia, we determined the role of specific PKC isozymes in ethanol-induced protection. We demonstrated that (i) brief exposure of isolated adult rat cardiac myocytes to 10-50 mM ethanol protected against damage induced by prolonged ischemia; (ii) an isozyme-selective ε PKC inhibitor developed in our laboratory inhibited the cardioprotective effect of acute ethanol exposure; (iii) protection of isolated intact adult rat heart also occurred after incubation with 10 mM ethanol 20 min before global ischemia; and (iv) ethanol-induced cardioprotection depended on PKC activation because it was blocked by chelerythrine and GF109203X, two PKC inhibitors. Consumption of 1-2 alcoholic beverages in humans leads to blood alcohol levels of ≈ 10 mM. Therefore, our work demonstrates that exposure to physiologically attainable ethanol levels minutes before ischemia provides cardioprotection that is mediated by direct activation of ε PKC in the cardiac myocytes. The potential clinical implications of our findings are discussed.
Editor: United States: National Academy of Sciences of the United States of America
Idioma: Inglês

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Cardioprotection from Ischemia by a Brief Exposure to Physiological Levels of Ethanol: Role of Epsilon Protein Kinase C

Chen, Che-Hong ; Gray, Mary O. ; Mochly-Rosen, Daria

United States: National Academy of Sciences of the United States of America

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