C-reactive protein augments hypoxia-induced apoptosis through mitochondrion-dependent pathway in cardiac myocytes |
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Authors: | Jin Yang Junhong Wang Shushu Zhu Xiangjian Chen Hengfang Wu Di Yang Jinan Zhang |
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Institution: | (1) Institute of Cardiovascular Disease, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China |
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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.
Jin Yang and Junhong Wang contributed equally to this work. |
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Keywords: | C-reactive protein Myocytes Infarction Apoptosis Mitochondria Bax Bcl-2 |
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