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SIRT1 deficiency attenuates MPP + ‐induced apoptosis in dopaminergic cells
Author(s) -
Park Geunyeong,
Jeong Joo-Won,
Kim Ja-Eun
Publication year - 2011
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.11.048
Subject(s) - sirtuin 1 , apoptosis , transfection , chemistry , cytotoxicity , sh sy5y , microbiology and biotechnology , nad+ kinase , activator (genetics) , resveratrol , poly adp ribose polymerase , neuroprotection , cell culture , biology , biochemistry , in vitro , downregulation and upregulation , pharmacology , enzyme , neuroblastoma , gene , genetics , polymerase
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.