SIRT1 deficiency attenuates MPP+-induced apoptosis in dopaminergic cells.
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.
Department of Pharmacology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Geunyeong
G
Park
Joo-Won
JW
Jeong
Ja-Eun
JE
Kim
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034622:RNA Interference; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C499184:BNIP2 protein, human; D002352:Carrier Proteins; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine