SIRT1 deficiency attenuates MPP+-induced apoptosis in dopaminergic cells

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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. © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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Park, G., Jeong, J. W., & Kim, J. E. (2011). SIRT1 deficiency attenuates MPP+-induced apoptosis in dopaminergic cells. FEBS Letters, 585(1), 219–224. https://doi.org/10.1016/j.febslet.2010.11.048

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