The role of hypoxia in the differentiation of P19 embryonal carcinoma cells into dopaminergic neurons.

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 1alpha (HIF-1alpha), based on its characteristic response to hypoxia. The result shows that HIF-1alpha mRNA level in P19 EC cells increases after hypoxia treatment. It is known that HIF-1alpha 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-1alpha up-regulation under hypoxia.