title: NAD(+) treatment prevents rotenone-induced apoptosis and necrosis of differentiated PC12 cells.
abstract: Nicotinamide adenine dinucleotide (NAD(+)) plays critical roles in not only energy metabolism and mitochondrial functions, but also calcium homeostasis and immunological functions. It has been reported that NAD(+) administration can reduce ischemic brain damage. However, the mechanisms underlying the protective effects remain unclear. Because mitochondrial impairments play a key role in the cell death in cerebral ischemia, in this study we tested our hypothesis that NAD(+) can decrease mitochondrial damage-induced cell death using differentiated PC12 cells as a cellular model. We found that NAD(+) can decrease both early-stage and late-stage apoptosis, as well as necrosis of rotenone-treated PC12 cells, as assessed by FACS-based Annexin V/AAD assay. We also found that NAD(+) treatment can restore the intracellular NAD(+) levels of the rotenone-treated cells. Moreover, NAD(+) treatment can prevent rotenone-induced mitochondria depolarization. In summary, our study has provided first direct evidence that NAD(+) treatment can prevent rotenone-induced apoptosis and necrosis. Our study has also indicated that NAD(+) treatment can prevent mitochondrial damage-induced cell death, which may at least partially result from its protective effects on rotenone-induced mitochondrial depolarization. Because both mitochondrial damage and apoptosis play key roles in multiple neurological disorders, our study has highlighted the therapeutic potential of NAD(+) for brain ischemia and other neurological diseases.
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, PR China.
authors.forename: Yunyi
authors.initials: Y
authors.lastname: Hong
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Nie
authors.affiliation: Department of Neurology, Third People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 201999, PR China.
authors.forename: Danhong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, PR China.
authors.forename: Xunbin
authors.initials: X
authors.lastname: Wei
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, PR China.
authors.forename: Xianting
authors.initials: X
authors.lastname: Ding
authors.affiliation: Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, PR China; Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China. Electronic address: weihaiy@sjtu.edu.cn.
authors.forename: Weihai
authors.initials: W
authors.lastname: Ying
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation; D007306:Insecticides / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009243:NAD / Q000378:metabolism / Q000494:pharmacology*; D009336:Necrosis; D016716:PC12 Cells; D051381:Rats; D012402:Rotenone / Q000633:toxicity*
chemical_list: D007306:Insecticides; D012402:Rotenone; D009243:NAD
keywords: Apoptosis; Mitochondrial membrane potential; NAD(+); Necrosis; PC12 cells; Rotenone