The Role of Hypoxia in the Differentiation of P19 Embryonal Carcinoma Cells into Dopaminergic Neurons |
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| Authors: | Li-Ying Wu Yue Wang Bing Jin Tong Zhao Hai-Tao Wu Yan Wu Ming Fan Xiao-Min Wang Ling-Ling Zhu |
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| Institution: | (1) Department of Brain Protection, Institute of Basic Medical Sciences, Beijing, 100850, People’s Republic of China;(2) Neuroscience Research Institute, Peking University, Beijing, China;(3) Department of Neurobiology, Capital University of Medicine, Beijing, China |
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| Abstract: | Nervous system development at early stage is in hypoxic environment. Very little is known about the role of hypoxia in neuronal
development. P19 embryonal carcinoma (EC) cells are a widely used model for studying early neuronal development. In this study
we investigated the roles of hypoxia in differentiation of dopaminergic neurons derived from P19 EC cells. Results demonstrate
that hypoxia increases the percentage of differentiated neurons, especially neurons of dopaminergic phenotype. To investigate
the potential mechanism involved in hypoxia promoted differentiation of dopaminergic neurons, we measured the expression of
hypoxia-inducible factor 1α (HIF-1α), based on its characteristic response to hypoxia. The result shows that HIF-1α mRNA level
in P19 EC cells increases after hypoxia treatment. It is known that HIF-1α regulates the expression of tyrosine hydroxylase
(TH) gene through binding to its promoter. Therefore, we propose that the underlying mechanism for hypoxia promoted differentiation
of dopaminergic neurons was mediated by HIF-1α up-regulation under hypoxia.
Yue Wang—Co-first author.
Special Issue in honor of Dr. Ji-Sheng Han. |
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| Keywords: | Hypoxia Dopaminergic neurons P19 EC cells TH HIF-1α |
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