SIRT1 deficiency attenuates MPP+-induced apoptosis in dopaminergic cells

Geunyeong Park; Joo Won Jeong; Ja Eun Kim

doi:10.1016/j.febslet.2010.11.048

SIRT1 deficiency attenuates MPP⁺-induced apoptosis in dopaminergic cells

Geunyeong Park
, Joo Won Jeong
, Ja Eun Kim

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

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.

Original language	English
Pages (from-to)	219-224
Number of pages	6
Journal	FEBS Letters
Volume	585
Issue number	1
DOIs	https://doi.org/10.1016/j.febslet.2010.11.048
Publication status	Published - 3 Jan 2011

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2010-0001754 ).

Keywords

1-Methyl-4-phenylpyridinium
Apoptosis
BNIP2
Parkinson's disease
Sirtuin 1

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10.1016/j.febslet.2010.11.048

Cite this

@article{e68d81215c0c411d9331563bddf6020d,

title = "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.",

keywords = "1-Methyl-4-phenylpyridinium, Apoptosis, BNIP2, Parkinson's disease, Sirtuin 1",

author = "Geunyeong Park and Jeong, \{Joo Won\} and Kim, \{Ja Eun\}",

note = "Funding Information: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2010-0001754 ).",

year = "2011",

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AU - Park, Geunyeong

AU - Jeong, Joo Won

AU - Kim, Ja Eun

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N2 - 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.

AB - 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.

KW - 1-Methyl-4-phenylpyridinium

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