Silencing of SIRT2 induces cell death and a decrease in the intracellular ATP level of PC12 cells.

Sirtuin 2 (SIRT2), a tubulin deacetylase, is a sirtuin family protein. SIRT2 inhibitors have been shown to decrease the cell death in cellular and Drosophila models of Parkinson's disease. However, SIRT2 decreases may also compromise cellular antioxidation capacity. Our current study found that silencing of SIRT2 led to a decrease in the intracellular ATP level of PC12 cells. We also found that AGK2, a selective SIRT2 inhibitor, can exacerbate H2O2-induced decreases in the intracellular ATP level of these cells. Our study further indicated that the reduction in SIRT2 level significantly increased necrosis of PC12 cells without affecting autophagy of the cells. These results suggest that SIRT2 is a key mediator of energy metabolism and basal survival of PC12 cells.