Abstract
C-reactive protein (CRP) is an important predictive factor for cardiac disorders including acute myocardial infarction. Therapeutic inhibition of CRP has been shown to be a promising new approach to cardioprotection in acute myocardial infarction in rat models, but the direct effects of CRP on cardiac myocytes are poorly defined. In this study, we investigated the effects of CRP on cardiac myocytes and its molecular mechanism involved. Neonatal rat cardiac myocytes were exposed to hypoxia for 8 h. Hypoxia induced myocyte apoptosis under serum-deprived conditions, which was accompanied by cytochrome c release from mitochondria into cytosol, as well as activation of Caspase-9, Caspase-3. Hypoxia also increased Bax and decreased Bcl-2 mRNA and protein expression, thereby significantly increasing Bax/Bcl-2 ratio. Cotreatment of CRP (100 μg/ml) under hypoxia significantly increased the percentage of apoptotic myocytes, translocation of cytochrome c, Bax/Bcl-2 ratio, and the activity of Caspase-9 and Caspase-3. However, no effects were observed on myocyte apoptosis when cotreatment of CRP under normoxia. Furthermore, Bcl-2 overexpression significantly improved cellular viability through inhibition of hypoxia or cotreatment with CRP induced Bax/Bcl-2 ratio changes and cytochrome c release from mitochondria to cytosol, and significantly blocked the activity of Caspase-9 and Caspase-3. The present study demonstrates that CRP could enhance apoptosis in hypoxia-stimulated myocytes through the mitochondrion-dependent pathway but CRP alone has no effects on neonatal rat cardiac myocytes under normoxia. Bcl-2 overexpression might prevent CRP-induced apoptosis by inhibiting cytochrome c release from the mitochondria and block activation of Caspase-9 and Caspase-3.
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Acknowledgments
This work was supported by National Natural Science Foundation of China (No. 30570745), Post-graduate Innovation Projects of Jiangsu Province (JX22013013), and “135” key laboratory of Jiangsu Province (SK200205). We also thank Dr. Wei Dong (Nanjing University, China) for his M-PEI.
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Jin Yang and Junhong Wang contributed equally to this work.
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Yang, J., Wang, J., Zhu, S. et al. C-reactive protein augments hypoxia-induced apoptosis through mitochondrion-dependent pathway in cardiac myocytes. Mol Cell Biochem 310, 215–226 (2008). https://doi.org/10.1007/s11010-007-9683-3
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DOI: https://doi.org/10.1007/s11010-007-9683-3