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Involvement of the ornithine decarboxylase/polyamine system in precondition-induced cardioprotection through an interaction with PKC in rat hearts

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Abstract

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. α-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-δ, -ε 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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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (30770878 and 30700288), the Technology Research Foundation of the Department of Education of Heilongjiang Province (11531076), the Technology Research Foundation of the Department of Health of Heilongjiang Province (2006-270), and the Youth Science and Technology Special Foundation in Heilongjiang Province (QC07C109).

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Authors and Affiliations

  1. Department of Pathophysiology, Harbin Medical University, 150086, Harbin, China

    Ya-Jun Zhao, Wei-Hua Zhang, Chang-Qing Xu, Hong-Zhu Li, Li-Na Wang, Hong Li, Yi-Hua Sun, Yan Lin, Li-Ping Han, Li Zhang & Yie Tian

  2. Department of Cardiology, The First Clinical Hospital of Harbin Medical University, 150001, Harbin, China

    Wei-Min Li

  3. Department of Biology, Lakehead University, Thunder Bay, ON, P7B 5E1, Canada

    Rui Wang

  4. Department of Pharmacology, Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, Harbin Medical University, 150086, Harbin, China

    Bao-Feng Yang

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  1. Ya-Jun Zhao
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Correspondence to Chang-Qing Xu or Wei-Min Li.

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Ya-Jun Zhao and Wei-Hua Zhang contributed equally to this study.

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Zhao, YJ., Zhang, WH., Xu, CQ. et al. Involvement of the ornithine decarboxylase/polyamine system in precondition-induced cardioprotection through an interaction with PKC in rat hearts. Mol Cell Biochem 332, 135–144 (2009). https://doi.org/10.1007/s11010-009-0183-5

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