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. Correspondence to Weihai Ying, PhD, School of Biomedical Engineering, Med-X Research Institute, Division of Disease Studies, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, People's Republic of China Tel: +86 216 293 3075; fax: +86 216 293 2302; e-mail: weihaiy@sjtu.edu.cn Received May 5, 2017 Accepted July 17, 2017 © 2017 Wolters Kluwer Health | Lippincott Williams & Wilkins

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