SIRT1 deficiency attenuates MPP+-induced apoptosis in dopaminergic cells.

ABSTRACT

One of the functions mediated by sirtuin 1 (SIRT1), the NAD(+)-dependent protein deacetylase, has been suggested to be neuroprotective since resveratrol, a SIRT1 activator, inhibits 1-methyl-4-phenylpyridinium ion (MPP(+))-induced cytotoxicity. In this study, we show that SIRT1 siRNA transfection blocks MPP(+)-induced apoptosis in SH-SY5Y cells. The ratio of potential pro-apoptotic BNIP2 to antiapoptotic BCL-xL was attenuated in SIRT1-deficient cells following MPP(+) treatment. In addition, BNIP2 shRNA-transfected cells showed reduced cleavage of PARP-1, while BNIP2 overexpression intensified the cleavage in MPP(+)-treated SH-SY5Y cells, suggesting that BNIP2 participates in the MPP(+)-induced apoptosis. Overall, these data imply that SIRT1 may mediate MPP(+)-induced cytotoxicity, possibly through the regulation of BNIP2.