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.