Fibroblast growth factor 9 activates anti-oxidative functions of Nrf2 through ERK signalling in striatal cell models of Huntington's disease

Issa Olakunle Yusuf, Hsiu Mei Chen, Pei Hsun Cheng, Chih Yi Chang, Shaw Jenq Tsai, Jih Ing Chuang, Chia Ching Wu, Bu Miin Huang, H. Sunny Sun, Shang Hsun Yang

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Huntington's disease (HD) is a heritable neurodegenerative disorder, and has been characterized as an increase of oxidative stress in brain regions. In our previous results, we showed fibroblast growth factor 9 (FGF9) provides neuroprotective functions to suppress cell death in HD striatal cells dominantly through ERK signalling. However, whether the working mechanism of FGF9 is related to anti-oxidative stress in HD is still unknown. In this study, STHdhQ7/Q7 (Q7) and STHdhQ111/Q111 (Q111) striatal knock-in cell lines were used to examine the neuroprotective effects of FGF9 against oxidative stress in HD. Results show that FGF9 alleviates oxidative stress induced by starvation in Q7 and Q111 cells. The treatment of FGF9 not only induces upregulation and activation of nuclear factor erythroid 2-like 2 (Nrf2), a critical transcription factor for anti-oxidative stress, but also further upregulates its downstream targets, such as superoxide dismutase 2, gamma-glutamylcysteine synthetase and glutathione reductase. Furthermore, blockage of the Nrf2 pathway abolishes the anti-oxidative functions of FGF9, and inhibition of ERK signalling reduces the activation of the FGF9-Nrf2 pathway, resulting in higher level of oxidative stress in HD cells. These results support the neuroprotective effects of FGF9 against oxidative stress through the ERK-Nrf2 pathway, and imply one of potential strategies for therapy of HD.

Original languageEnglish
Pages (from-to)256-266
Number of pages11
JournalFree Radical Biology and Medicine
Volume130
DOIs
Publication statusPublished - 2019 Jan

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

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