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Treadmill exercise activates Nrf2 antioxidant system to protect the nigrostriatal dopaminergic neurons from MPP(+) toxicity.
MedLine Citation:
PMID:  25286336     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Exercise induces oxidative stress, which may activate adaptive antioxidant responses. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in the defense of oxidative stress by regulating the expression of antioxidant enzymes, gamma-glutamylcysteine ligase (γGCL) and heme oxygenase-1 (HO-1). We investigated whether treadmill exercise protects dopaminergic neurons by regulating the Nrf2 antioxidant system in a 1-methyl-4-phenylpyridine (MPP(+))-induced parkinsonian rat model. We found that MPP(+) induced early decreases in total glutathione level and Nrf2/γGCLC (catalytic subunit of γGCL) expression, but late upregulation of HO-1 expression in association with loss of nigral dopaminergic neurons and downregulation of tyrosine hydroxylase and dopamine transporter expression in the striatum. Treadmill exercise for 4weeks induced upregulation of Nrf2 and γGCLC expression, and also prevented the MPP(+)-induced downregulation of Nrf2/γGCLC/glutathione, HO-1 upregulation, and nigrostriatal dopaminergic neurodegeneration. Moreover, the protective effect of exercise was blocked by the knockdown of Nrf2 using a lentivirus-carried shNrf2 delivery system. These results demonstrate an essential role of Nrf2 in the exercise-mediated protective effect that exercise enhances the nigrostriatal Nrf2 antioxidant defense capacity to protect dopaminergic neurons against the MPP(+)-induced toxicity.
Authors:
Yi-Hsien Tsou; Ching-Ting Shih; Cheng-Hsin Ching; Jui-Yen Huang; Chauying J Jen; Lung Yu; Yu-Min Kuo; Fong-Sen Wu; Jih-Ing Chuang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-3
Journal Detail:
Title:  Experimental neurology     Volume:  -     ISSN:  1090-2430     ISO Abbreviation:  Exp. Neurol.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-6     Completed Date:  -     Revised Date:  2014-10-7    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Inc.
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