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Nitric oxide and oxygen radicals induced apoptosis via bcl-2 and p53 pathway in hypoxia-reoxygenated cardiomyocytes

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Abstract

Neonatal rat cardiomyocytes were subjected to 24 h of hypoxia 95%N2/5%CO2 and 24 h of hypoxia plus 4 h of reoxygenation 95%O2/5%CO2. 24 h of hypoxia increased the levels of NO, NO2 -/NO3 -, TBARS and LDH. 24 h of hypoxia plus 4 h of reoxygenation decreased the levels of NO, NO2 -/NO3 -, but further increased TBARS and LDH. The hypoxia up-regulated the expression of bcl-2, p53 and p21/waf1/cip1 but the reoxygenation down-regulated the expression of bcl-2, and further up-regulated p53 and p21/waf1/cip1. The hypoxia increased cell apoptosis and reoxygenation further increased both apoptotic and necrotic cell death. NO, NO2/NO3 - TBARS, DNA fragmentation and cell apoptosis were enhanced by SNP and inhibited by L-NAME respectively. In addition, SOD/catalase down-regulated the expression of p53, p21/wafl/cipl and TBARS but up-regulated bcl-2 and increased indirectly the level of NO, NO2 -/NO3 -, and inhibited DNA fragmentation. The results suggest that hypoxia-induced cell death is associated with the activation of NO, bcl-2 and p53 pathway, while hypoxia-reoxygenation induced cell death via the generation of reactive oxygen species and activation of p53 pathway. The present study clarified that NO may be an initiative signal to apoptotic cell death and the activation of bcl-2, p53 and p21/waf1/cip1 pathway in hypoxic and hypoxia-reoxygenated cardiomyocytes.

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Authors and Affiliations

  1. Laboratory of Visual Information Processing, Center for Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, 100101, Beijing, China

    Jiangang Shen, Deliang Zhang, Wenjuan Xin & Baolu Zhao

  2. Institute of Chinese Medicine, First Military Medical University, 510515, Guangzhou, China

    Jiangang Shen, Xingshen Qiu & Bo Jiang

  3. Division of Medical Physics, Department of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong, China

    Peter C. W. Fung

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  1. Jiangang Shen
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  2. Xingshen Qiu
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  3. Bo Jiang
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  4. Deliang Zhang
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  5. Wenjuan Xin
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  6. Peter C. W. Fung
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  7. Baolu Zhao
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Correspondence to Baolu Zhao.

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Shen, J., Qiu, X., Jiang, B. et al. Nitric oxide and oxygen radicals induced apoptosis via bcl-2 and p53 pathway in hypoxia-reoxygenated cardiomyocytes. Sci. China Ser. C.-Life Sci. 46, 28–39 (2003). https://doi.org/10.1007/BF03182682

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  • DOI: https://doi.org/10.1007/BF03182682

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