Peroxisome proliferator-activated receptor alpha accelerates neuronal differentiation and this might involve the mitogen-activated protein kinase pathway
Autor: | Yi Ping Huang, Pei Yi Chen, Chingju Lin, Nai-Wen Chang, Hsu Chin Chan |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
MAPK/ERK pathway Prostaglandins E Synthetic Teratocarcinoma Time Factors p38 mitogen-activated protein kinases Peroxisome proliferator-activated receptor Tretinoin Nestin 03 medical and health sciences 0302 clinical medicine Developmental Neuroscience Cell Movement Cell Line Tumor Humans PPAR alpha chemistry.chemical_classification NeuroD Neurons Analysis of Variance biology Chemistry Cyclin-dependent kinase 5 Cell Differentiation Cyclin-Dependent Kinase 5 Cell biology Gene Expression Regulation Neoplastic 030104 developmental biology nervous system Mitogen-activated protein kinase biology.protein Peroxisome proliferator-activated receptor alpha Microtubule-Associated Proteins 030217 neurology & neurosurgery Developmental Biology Signal Transduction |
Zdroj: | International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. 71 |
ISSN: | 1873-474X |
Popis: | Activation of peroxisome proliferator-activated receptor alpha (PPARα) has been reported to modulate cell proliferation, migration, and differentiation in astrocytes. In this study, we used a retinoic acid (RA)-induced differentiation model of NTERA-2/clone D1 (NT2) cells to explore the functional significance of PPARα in neuronal differentiation. We found that activating PPARα by Wy14643 accelerated neuronal differentiation via regulating the expression of neuronal markers. RT-PCR assays showed a significant increase in NeuroD expression and a decrease in nestin expression in cells treated concomitantly with RA and Wy14643 for 2 days compared to the levels in cells treated with RA alone. Expression of MAP2 protein, a mature neuronal marker, was markedly upregulated at day 10 of Wy14643 treatment, which was maintained after 21 days of neuronal formation. Corresponding to the changes in MAP2 expression, the expression of Cdk5 was upregulated with Wy14643 exposure from day 10 to day 21. Moreover, cells treated with Wy14643 displayed higher expression levels of phospho-ERK and phospho-p38 in the differentiation process than cell treated with RA alone. These results indicated that activation of PPARα accelerated neuronal differentiation through upregulating the expression of NeuroD, MAP2, and Cdk5 and downregulating the expression of nestin. MAPK signals, ERK and p38, might contribute to the accelerated differentiation process. These findings suggest that PPARα plays a role in regulating neuronal differentiation and may be beneficial for functional recovery from neurological disorders. |
Databáze: | OpenAIRE |
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