TY - JOUR
T1 - Fibroblast growth factor 9 activates anti-oxidative functions of Nrf2 through ERK signalling in striatal cell models of Huntington's disease
AU - Yusuf, Issa Olakunle
AU - Chen, Hsiu Mei
AU - Cheng, Pei Hsun
AU - Chang, Chih Yi
AU - Tsai, Shaw Jenq
AU - Chuang, Jih Ing
AU - Wu, Chia Ching
AU - Huang, Bu Miin
AU - Sun, H. Sunny
AU - Yang, Shang Hsun
N1 - Funding Information:
This work was supported by the Ministry of Science and Technology, Taiwan ( MOST 105–2628-B-006–015-MY3 and MOST 106–2320-B-006-004 ).
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85056467868&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056467868&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2018.10.455
DO - 10.1016/j.freeradbiomed.2018.10.455
M3 - Article
C2 - 30391672
AN - SCOPUS:85056467868
SN - 0891-5849
VL - 130
SP - 256
EP - 266
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -