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

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1099-1108
Number of pages10
JournalFree Radical Biology and Medicine
Volume49
Issue number6
DOIs
Publication statusPublished - 2010 Sept

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Fingerprint

Dive into the research topics of 'Fibroblast growth factor 9 upregulates heme oxygenase-1 and γ-glutamylcysteine synthetase expression to protect neurons from 1-methyl-4-phenylpyridinium toxicity'. Together they form a unique fingerprint.

Cite this