期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 332, 期 1-2, 页码 135-144出版社
SPRINGER
DOI: 10.1007/s11010-009-0183-5
关键词
Ischemic preconditioning; Polyamine; Protein kinase C; Ornithine decarboxylase
类别
资金
- National Natural Science Foundation of China [30770878, 30700288]
- Technology Research Foundation of the Department of Education of Heilongjiang Province [11531076]
- Technology Research Foundation of the Department of Health of Heilongjiang Province [2006-270]
- Youth Science and Technology Special Foundation in Heilongjiang Province [QC07C109]
Polyamines (putrescine, spermidine, and spermine) play an essential role in cell growth, differentiation, and apoptosis. Protein kinase C (PKC) stimulates polyamine biosynthesis through the induction of ornithine decarboxylase (ODC), a rate-limiting enzyme in polyamine biosynthesis. Activation of PKC mediates ischemic preconditioning to reduce necrosis and apoptosis in intact hearts and in isolated culture cardiomyocytes. In this study, we examined whether the ODC/polyamine system is involved in the ischemic preconditioning signaling pathway and whether this system interacts with PKC in preconditioning-induced cardioprotection. Hearts were preconditioned with three cycles of 5-min ischemia and 5-min reflow, which caused an increase of ODC expression and spermidine, spermine, and total polyamine pool levels. alpha-Difluoromethylornithine (DFMO) and ethylglyoxal bis (guanylhydrazone) (EGBG) inhibited the key enzymes involved in polyamine biosynthesis, and abolished the preconditioning-induced reduction in infarct size and improvement in postischemic heart contractility function. They also increased cell apoptosis extent and aggravated myocardium ultrastructure damage. Inhibition also attenuated the preconditioning-induced translocation and activation of the PKC-delta, -epsilon isoforms from the cytosol to the particulate. Conversely, activation of PKC by phorbol 12-myristate 13-acetate (PMA) upregulated the ODC/polyamine system, whereas the PKC inhibitor chelerythrine (Che) downregulated the ODC/polyamine system. These findings suggest that upregulation of the polyamine synthesis metabolism occurs in response to preconditioning and mediates preconditioning-induced cardioprotection. The ODC/polyamine system and PKC signals may cross-talk in preconditioned hearts such that inhibiting one pathway leads to a reduction in the activity of the other pathway and vice versa.
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