Abstract
Exposure to xenobiotics has a significant impact in brain physiology, that could be liked to an excitotoxic processes induced by a massive release of the main excitatory neurotransmitter, L-glutamate. Overstimulation of post-synaptic and extra-synaptic glutamate receptors leads to a disturbance of intracellular calcium homeostasis that is critically involved in neuronal death. Hence, glutamate extracellular levels are tightly regulated through its uptake by glial glutamate transporters. It has been observed that glutamate regulates its own removal, both in the short-time frame via a transporter-mediated decrease in the uptake, and in the long-term through the transcriptional control of its gene expression, a process mediated by glutamate receptors that involves the Ca2+/diacylglycerol-dependent protein kinase and the transcription factor Ying Yang 1. Taking into consideration that this transcription factor is as a member of the Polycomb complex and thus, part of repressive and activating chromatin remodeling factors, it might direct the interaction of DNA methyltransferases or dioxygenases of methylated cytosines to their target sequences. Since glial glutamate transporters promoters are targets of Ying-Yang 1, in this contribution, we explored the role of dynamic DNA methylation in the expression and function of glial glutamate transporters. To this end, we used the well-characterized models of primary cultures of chick cerebellar Bergmann glia cells and a human retina-derived Müller glia cell line. A time and dose-dependent increase in global DNA methylation was found upon glutamate exposure. Under hypomethylation conditions, both glial glutamate transporters expression and function were increased. These results, favor the notion that a dynamic methylation program triggered by glutamate in glia cells modulates one of its major functions: glutamate removal.
DNA Methylation-Dependent Translational Control of Glutamate Transporters in Cultured Radial Glia Cells
