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RETRACTED ARTICLE

Sirtuin 2 (SIRT2) enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal damage via deacetylating forkhead box O3a (Foxo3a) and activating Bim protein.
J Biol Chem. 2012 Sep 21; 287(39):32307-11.JB

Abstract

Sirtuins are NAD-dependent protein deacetylases that were shown to have beneficial effects against age-related diseases. SIRT2 is a strong deacetylase that is highly expressed in brain. It has been associated with neurodegenerative diseases. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a dopaminergic neurotoxin that replicates most of the clinical features of Parkinson disease (PD) and produces a reliable and reproducible lesion of the nigrostriatal dopaminergic pathway and neurodegeneration after its systemic administration. Chronic administration of MPTP induces lesion via apoptosis. We show here that SIRT2 deacetylates Foxo3a, increases RNA and protein levels of Bim, and as a result, enhances apoptosis in the MPTP model of PD. We also show that neurodegeneration induced by chronic MPTP regimen is prevented by genetic deletion of SIRT2 in mouse. Deletion of SIRT2 leads to the reduction of apoptosis due to an increase in acetylation of Foxo3a and a decrease in Bim levels. We demonstrate that SIRT2 deacetylates Foxo3a, activates Bim, and induces apoptosis only in 1-methyl-4-phenylpyridinium-treated cells. Therefore, designing SIRT2 inhibitors might be helpful to develop effective treatments for PD.

Links

Publisher Full Text
ncbi.nlm.nih.gov
linkinghub.elsevier.com
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Authors+Show Affiliations

Liu L
Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Arun A
No affiliation info available
Ellis L
No affiliation info available
Peritore C
No affiliation info available
Donmez G
No affiliation info available

MeSH

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineAcetylationAnimalsApoptosisApoptosis Regulatory ProteinsBcl-2-Like Protein 11Forkhead Box Protein O3Forkhead Transcription FactorsMPTP PoisoningMembrane ProteinsMiceMice, KnockoutNerve Tissue ProteinsNeurotoxinsParkinson Disease, SecondaryProto-Oncogene ProteinsSirtuin 2Striatonigral DegenerationSubstantia Nigra

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Retracted Publication

Language

eng

PubMed ID

22898818

Citation

Liu, Lei, et al. "Sirtuin 2 (SIRT2) Enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Nigrostriatal Damage Via Deacetylating Forkhead Box O3a (Foxo3a) and Activating Bim Protein." The Journal of Biological Chemistry, vol. 287, no. 39, 2012, pp. 32307-11.
Liu L, Arun A, Ellis L, et al. Sirtuin 2 (SIRT2) enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal damage via deacetylating forkhead box O3a (Foxo3a) and activating Bim protein. J Biol Chem. 2012;287(39):32307-11.
Liu, L., Arun, A., Ellis, L., Peritore, C., & Donmez, G. (2012). Sirtuin 2 (SIRT2) enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal damage via deacetylating forkhead box O3a (Foxo3a) and activating Bim protein. The Journal of Biological Chemistry, 287(39), 32307-11.
Liu L, et al. Sirtuin 2 (SIRT2) Enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Nigrostriatal Damage Via Deacetylating Forkhead Box O3a (Foxo3a) and Activating Bim Protein. J Biol Chem. 2012 Sep 21;287(39):32307-11. PubMed PMID: 22898818.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sirtuin 2 (SIRT2) enhances 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal damage via deacetylating forkhead box O3a (Foxo3a) and activating Bim protein. AU - Liu,Lei, AU - Arun,Anirudh, AU - Ellis,Lakia, AU - Peritore,Carina, AU - Donmez,Gizem, Y1 - 2012/08/16/ PY - 2012/8/18/entrez PY - 2012/8/18/pubmed PY - 2012/12/12/medline SP - 32307 EP - 11 JF - The Journal of biological chemistry JO - J Biol Chem VL - 287 IS - 39 N2 - Sirtuins are NAD-dependent protein deacetylases that were shown to have beneficial effects against age-related diseases. SIRT2 is a strong deacetylase that is highly expressed in brain. It has been associated with neurodegenerative diseases. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a dopaminergic neurotoxin that replicates most of the clinical features of Parkinson disease (PD) and produces a reliable and reproducible lesion of the nigrostriatal dopaminergic pathway and neurodegeneration after its systemic administration. Chronic administration of MPTP induces lesion via apoptosis. We show here that SIRT2 deacetylates Foxo3a, increases RNA and protein levels of Bim, and as a result, enhances apoptosis in the MPTP model of PD. We also show that neurodegeneration induced by chronic MPTP regimen is prevented by genetic deletion of SIRT2 in mouse. Deletion of SIRT2 leads to the reduction of apoptosis due to an increase in acetylation of Foxo3a and a decrease in Bim levels. We demonstrate that SIRT2 deacetylates Foxo3a, activates Bim, and induces apoptosis only in 1-methyl-4-phenylpyridinium-treated cells. Therefore, designing SIRT2 inhibitors might be helpful to develop effective treatments for PD. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/22898818/Sirtuin_2__SIRT2__enhances_1_methyl_4_phenyl_1236_tetrahydropyridine__MPTP__induced_nigrostriatal_damage_via_deacetylating_forkhead_box_O3a__Foxo3a__and_activating_Bim_protein_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)62893-9 DB - PRIME DP - Unbound Medicine ER -
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