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PMID:9388241

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Citation

Gray, MO, Karliner, JS and Mochly-Rosen, D (1997) A selective epsilon-protein kinase C antagonist inhibits protection of cardiac myocytes from hypoxia-induced cell death. J. Biol. Chem. 272:30945-51

Abstract

Protein kinase C activation is thought to protect cardiac tissue from subsequent ischemic injury by a process termed preconditioning. The protein kinase C isozyme that mediates preconditioning has not yet been identified. Using a cell culture model of hypoxic preconditioning, we found that cardiac myocyte viability after 9 h of hypoxia was increased by more than 50% over control. Preconditioning activated protein kinase C isozymes as evidenced by translocation from one cell compartment to another as follows: there was a 2.1-fold increase in epsilon-protein kinase C activation, a 2. 8-fold increase in delta-protein kinase C activation, and no increase in betaI-protein kinase C activation. 4beta-Phorbol 12-myristate 13-acetate mimicked hypoxic preconditioning, increasing myocyte survival after prolonged hypoxia by 34% compared with control. We previously identified an epsilon-protein kinase C-selective antagonist, epsilonV1-2 peptide, that inhibits epsilon-protein kinase C translocation and function in cardiac myocytes (Johnson, J. A., Gray, M. O., Chen, C.-H., and Mochly-Rosen, D. (1996) J. Biol. Chem. 271, 24962-24966). epsilonV1-2 peptide abolished hypoxic preconditioning and phorbol ester-mediated cardiac protection. Therefore, preconditioning can be induced in this culture model, and activation of epsilon-protein kinase C is critical for cardiac myocyte protection.

Links

PubMed

Keywords

Animals; Biological Transport/drug effects; Cell Death/drug effects; Cell Hypoxia/drug effects; Cells, Cultured; Enzyme Activation/drug effects; Enzyme Inhibitors/pharmacology; HSP70 Heat-Shock Proteins/metabolism; Heart/drug effects; Ischemic Preconditioning, Myocardial; Isoenzymes/antagonists & inhibitors; Isoenzymes/physiology; Microscopy, Fluorescence; Myocardium/cytology; Peptide Fragments/pharmacology; Protein Kinase C/antagonists & inhibitors; Protein Kinase C/physiology; Protein Kinase C-epsilon; Rats; Tetradecanoylphorbol Acetate/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:BAD

GO:1990051: activation of protein kinase C activity

ECO:0000314:

P

Figure 2

complete
CACAO 9429

See also

References

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