GCLC公司
GCLM公司
下调和上调
多巴胺能
氧化应激
谷胱甘肽
化学
神经退行性变
抗氧化剂
酪氨酸羟化酶
神经保护
药理学
多巴胺
内科学
内分泌学
生物
生物化学
医学
酶
基因
疾病
作者
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
标识
DOI:10.1016/j.expneurol.2014.09.021
摘要
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 4 weeks 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.
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