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NAD+ Treatment Can Prevent Rotenone-Induced Increases in DNA Damage, Bax Levels and Nuclear Translocation of Apoptosis-Inducing Factor in Differentiated PC12 Cells

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Abstract

Nicotinamide adenine dinucleotide (NAD+) plays critical roles in energy metabolism, mitochondrial functions, calcium homeostasis and immunological functions. Our previous studies have found that NAD+ administration can profoundly decrease ischemic brain injury and traumatic brain injury. Our recent study has also provided first direct evidence indicating that NAD+ treatment can decrease cellular apoptosis, while the mechanisms underlying this protective effect remain unclear. In our current study, we determined the effects of NAD+ treatment on several major factors in apoptosis and necrosis, including levels of Bax and nuclear translocation of apoptosis-inducing factor (AIF), as well as levels of DNA double-strand breaks (DSBs) and intracellular ATP in rotenone-treated differentiated PC12 cells. We found that NAD+ treatment can markedly attenuate the rotenone-induced increases in the levels of Bax and nuclear translocation of AIF in the cells. We further found that NAD+ treatment can significantly attenuate the rotenone-induced increase in the levels of DSBs and decrease in the intracellular ATP levels. Collectively, our study has suggested mechanisms underlying the preventive effects of NAD+ on apoptosis, which has highlighted the therapeutic potential of NAD+ for decreasing apoptotic changes in multiple major diseases.

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Acknowledgments

This study was supported by Chinese National Science Foundation Grants #81171098 and #81271305 (to W. Y.), and two Shanghai Jiao Tong University Grants for Interdisciplinary Research on Medicine and Engineering (to W. Y.).

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Authors and Affiliations

  1. Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai, 200030, People’s Republic of China

    Yunyi Hong, Hui Nie, Xunbin Wei & Weihai Ying

  2. Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China

    Weihai Ying

  3. Radiation Oncology Department, Shanghai Proton and Heavy Ion Center, Shanghai, 201321, People’s Republic of China

    Shen Fu

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  1. Yunyi Hong
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  2. Hui Nie
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  3. Xunbin Wei
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  4. Shen Fu
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  5. Weihai Ying
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Correspondence to Weihai Ying.

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Hong, Y., Nie, H., Wei, X. et al. NAD+ Treatment Can Prevent Rotenone-Induced Increases in DNA Damage, Bax Levels and Nuclear Translocation of Apoptosis-Inducing Factor in Differentiated PC12 Cells. Neurochem Res 40, 837–842 (2015). https://doi.org/10.1007/s11064-015-1534-0

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  • DOI: https://doi.org/10.1007/s11064-015-1534-0

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