Tags

Type your tag names separated by a space and hit enter

Deprenyl prevents MPP(+)-induced oxidative damage in PC12 cells by the upregulation of Nrf2-mediated NQO1 expression through the activation of PI3K/Akt and Erk.
Toxicology. 2011 Dec 18; 290(2-3):286-94.T

Abstract

Neuroprotection has been the focus of several current efforts to develop a strategy for the treatment of Parkinson's disease (PD). The B-type monoamine oxidase (MAO-B) inhibitor deprenyl (selegiline) is used clinically as a PD therapeutic agent, however, its cytoprotective mechanism has not yet been fully elucidated. In this study, we show that deprenyl upregulates the expression and activity of NAD(P)H: quinone oxidoreductase 1 (NQO1), attenuates the increase in the quinoprotein levels in 1-methyl-4-phenylpyridinium (MPP(+))-treated PC12 cells, and protects PC12 cells from oxidative damage. Deprenyl triggers the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway by increasing the nuclear translocation and DNA-binding activity of Nrf2. Both the antioxidant activity of deprenyl and its effect on NQO1 upregulation were greatly attenuated in Nrf2 siRNA transfected cells. The phosphorylation of extracellular regulating protein kinase (Erk) and Akt can be induced by the administration of 50μM deprenyl in PC12 cells, and the ability of deprenyl to enhance NQO1 expression and Nrf2 nuclear translocation is partly attenuated by the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 and is almost completely attenuated by the phosphatidyl-inositol 3 kinase (PI3K) inhibitor LY294002. The activation of Nrf2/ARE signaling by deprenyl in PC12 cells is independent of MAO-B inhibition. Altogether, our findings indicate that deprenyl protects PC12 cells exposed to MPP(+) resulting from oxidative stress via the Nrf2-mediated upregulation of NQO1 involving both the PI3K/Akt and Erk pathways.

Authors+Show Affiliations

Department of Neurology, Shenzhen Nanshan Hospital, Shenzhen 518052, People's Republic of China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22019741

Citation

Xiao, Haibing, et al. "Deprenyl Prevents MPP(+)-induced Oxidative Damage in PC12 Cells By the Upregulation of Nrf2-mediated NQO1 Expression Through the Activation of PI3K/Akt and Erk." Toxicology, vol. 290, no. 2-3, 2011, pp. 286-94.
Xiao H, Lv F, Xu W, et al. Deprenyl prevents MPP(+)-induced oxidative damage in PC12 cells by the upregulation of Nrf2-mediated NQO1 expression through the activation of PI3K/Akt and Erk. Toxicology. 2011;290(2-3):286-94.
Xiao, H., Lv, F., Xu, W., Zhang, L., Jing, P., & Cao, X. (2011). Deprenyl prevents MPP(+)-induced oxidative damage in PC12 cells by the upregulation of Nrf2-mediated NQO1 expression through the activation of PI3K/Akt and Erk. Toxicology, 290(2-3), 286-94. https://doi.org/10.1016/j.tox.2011.10.007
Xiao H, et al. Deprenyl Prevents MPP(+)-induced Oxidative Damage in PC12 Cells By the Upregulation of Nrf2-mediated NQO1 Expression Through the Activation of PI3K/Akt and Erk. Toxicology. 2011 Dec 18;290(2-3):286-94. PubMed PMID: 22019741.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Deprenyl prevents MPP(+)-induced oxidative damage in PC12 cells by the upregulation of Nrf2-mediated NQO1 expression through the activation of PI3K/Akt and Erk. AU - Xiao,Haibing, AU - Lv,Feng, AU - Xu,Wuping, AU - Zhang,Linhong, AU - Jing,Ping, AU - Cao,Xu, Y1 - 2011/10/15/ PY - 2011/04/03/received PY - 2011/10/08/revised PY - 2011/10/10/accepted PY - 2011/10/25/entrez PY - 2011/10/25/pubmed PY - 2012/1/13/medline SP - 286 EP - 94 JF - Toxicology JO - Toxicology VL - 290 IS - 2-3 N2 - Neuroprotection has been the focus of several current efforts to develop a strategy for the treatment of Parkinson's disease (PD). The B-type monoamine oxidase (MAO-B) inhibitor deprenyl (selegiline) is used clinically as a PD therapeutic agent, however, its cytoprotective mechanism has not yet been fully elucidated. In this study, we show that deprenyl upregulates the expression and activity of NAD(P)H: quinone oxidoreductase 1 (NQO1), attenuates the increase in the quinoprotein levels in 1-methyl-4-phenylpyridinium (MPP(+))-treated PC12 cells, and protects PC12 cells from oxidative damage. Deprenyl triggers the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway by increasing the nuclear translocation and DNA-binding activity of Nrf2. Both the antioxidant activity of deprenyl and its effect on NQO1 upregulation were greatly attenuated in Nrf2 siRNA transfected cells. The phosphorylation of extracellular regulating protein kinase (Erk) and Akt can be induced by the administration of 50μM deprenyl in PC12 cells, and the ability of deprenyl to enhance NQO1 expression and Nrf2 nuclear translocation is partly attenuated by the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 and is almost completely attenuated by the phosphatidyl-inositol 3 kinase (PI3K) inhibitor LY294002. The activation of Nrf2/ARE signaling by deprenyl in PC12 cells is independent of MAO-B inhibition. Altogether, our findings indicate that deprenyl protects PC12 cells exposed to MPP(+) resulting from oxidative stress via the Nrf2-mediated upregulation of NQO1 involving both the PI3K/Akt and Erk pathways. SN - 1879-3185 UR - https://www.unboundmedicine.com/medline/citation/22019741/Deprenyl_prevents_MPP_+__induced_oxidative_damage_in_PC12_cells_by_the_upregulation_of_Nrf2_mediated_NQO1_expression_through_the_activation_of_PI3K/Akt_and_Erk_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(11)00446-X DB - PRIME DP - Unbound Medicine ER -