Fibroblast Growth Factor 9 Suppresses Striatal Cell Death Dominantly Through ERK Signaling in Huntington's Disease

Autor: H. Sunny Sun, Issa Olakunle Yusuf, Hsiu Mei Chen, Chih Yi Chang, Jih Ing Chuang, Yu Fan Chang, Chia Wei Lin, Shang Hsun Yang, Han In Yang, Pei Hsun Cheng, Chia Ching Wu, Bu Miin Huang, Shaw Jenq Tsai
Rok vydání: 2018
Předmět:
0301 basic medicine
MAPK/ERK pathway
Fibroblast Growth Factor 9
Cell signaling
Programmed cell death
Striatal cell death
Physiology
MAP Kinase Signaling System
bcl-X Protein
Apoptosis
Mice
Transgenic
Biology
Neuroprotection
lcsh:Physiology
Cell Line
lcsh:Biochemistry
03 medical and health sciences
Mice
Huntington's disease
Neurotrophic factors
Nitriles
medicine
Glial cell line-derived neurotrophic factor
Butadienes
Animals
lcsh:QD415-436
Glial Cell Line-Derived Neurotrophic Factor
Extracellular Signal-Regulated MAP Kinases
Protein kinase B
Visual Cortex
lcsh:QP1-981
Cell growth
Caspase 3
JNK Mitogen-Activated Protein Kinases
medicine.disease
stomatognathic diseases
030104 developmental biology
Huntington Disease
Cancer research
biology.protein
Proto-Oncogene Proteins c-akt
Huntington’s disease
Zdroj: Cellular Physiology and Biochemistry, Vol 48, Iss 2, Pp 605-617 (2018)
ISSN: 1421-9778
Popis: Background/Aims: Huntington’s disease (HD) is a heritable neurodegenerative disorder, and there is no cure for HD to date. A type of fibroblast growth factor (FGF), FGF9, has been reported to play prosurvival roles in other neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. However, the effects of FGF9 on HD is still unknown. With many similarities in the cellular and pathological mechanisms that eventually cause cell death in neurodegenerative diseases, we hypothesize that FGF9 might provide neuroprotective functions in HD. Methods: In this study, STHdhQ7/Q7 (WT) and STHdhQ111/Q111 (HD) striatal knock-in cell lines were used to evaluate the neuroprotective effects of FGF9. Cell proliferation, cell death and neuroprotective markers were determined via the MTT assay, propidium iodide staining and Western blotting, respectively. The signaling pathways regulated by FGF9 were demonstrated using Western blotting. Additionally, HD transgenic mouse models were used to further confirm the neuroprotective effects of FGF9 via ELISA, Western blotting and immunostaining. Results: Results show that FGF9 not only enhances cell proliferation, but also alleviates cell death as cells under starvation stress. In addition, FGF9 significantly upregulates glial cell line-derived neurotrophic factor (GDNF) and an anti-apoptotic marker, Bcl-xL, and decreases the expression level of an apoptotic marker, cleaved caspase 3. Furthermore, FGF9 functions through ERK, AKT and JNK pathways. Especially, ERK pathway plays a critical role to influence the effects of FGF9 toward cell survival and GDNF production. Conclusions: These results not only show the neuroprotective effects of FGF9, but also clarify the critical mechanisms in HD cells, further providing an insight for the therapeutic potential of FGF9 in HD.
Databáze: OpenAIRE
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