SIRT2 and Akt mediate NAD+-induced and NADH-induced increases in the intracellular ATP levels of BV2 microglia under basal conditions

NAD replenishment can restore ATP levels and rescue premature aging in Cockayne syndrome mice. However, there has been no mechanistic study regarding the effects of NAD and NADH on intracellular ATP levels under basal conditions. In our current study, we used BV2 microglia to test our hypothesis that NAD and NADH can increase intracellular ATP levels under basal conditions. We found that both NAD and NADH significantly increased the intracellular ATP levels of BV2 microglia, which were attenuated by SIRT2 siRNA, the SIRT2 inhibitor AGK2, and the phosphatidylinositol 3-kinase/Akt inhibitor LY294002. Our study has also suggested that SIRT2 mediates the NAD-induced and NADH-induced increase in Akt phosphorylation in BV2 microglia. Collectively, our study has suggested that SIRT2 mediates both NAD-induced and NADH-induced increases in the intracellular ATP levels of BV2 microglia by modulating Akt phosphorylation.