Fibroblast growth factor 9 upregulates heme oxygenase-1 and γ-glutamylcysteine synthetase expression to protect neurons from 1-methyl-4-phenylpyridinium toxicity

Jui Yen Huang, Jih Ing Chuang

研究成果: Article

22 引文 斯高帕斯(Scopus)

摘要

Oxidative stress and lower levels of trophic factors involved in nigrostriatal dopaminergic neurodegeneration are a hallmark of Parkinson disease. Our previous studies found that fibroblast growth factor 9 (FGF9) prevented 1-methyl-4-phenylpyridinium (MPP+)-induced nigral dopaminergic neuron death and was involved in the neuroprotection of the antioxidant melatonin. However, the protective mechanisms mediated by FGF9 remain unclear. Herein, we explored whether FGF9 regulated the cellular antioxidant defense protecting dopaminergic neurons against MPP+ intoxication. We found that FGF9 treatment alone induced a decrease in hydrogen peroxide (H2O2) level, an increase in glutathione content, and an upregulation of γ-glutamylcysteine synthetase (γ-GCS) and heme oxygenase 1 (HO-1) expression in primary cortical neurons but not in astrocytes. Simultaneous treatment with FGF9 and MPP+ prevented MPP+-induced neuron death and H2O2 overproduction but did not affect the FGF9-increased γ-GCS and HO-1 protein expression. Inhibition of γ-GCS or HO-1 prevented the inhibitory effect of FGF9 on MPP+-induced H2O2 production and death in mesencephalic dopaminergic and cortical neurons. However, in the absence of MPP+, the FGF9-induced H2O2 reduction was blocked by HO-1 inhibitors, but not by γ-GCS inhibitors. These results indicate that FGF9 upregulates γ-GCS and HO-1 expression to protect cortical and dopaminergic neurons from MPP+-induced oxidative insult.

原文English
頁(從 - 到)1099-1108
頁數10
期刊Free Radical Biology and Medicine
49
發行號6
DOIs
出版狀態Published - 2010 九月 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

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