Transcriptional regulation of PSA-NCAM expression by NMDA receptor activation in RA-differentiated C6 glioma cultures - PubMed (original) (raw)

Transcriptional regulation of PSA-NCAM expression by NMDA receptor activation in RA-differentiated C6 glioma cultures

Jaspreet Singh et al. Brain Res Bull. 2009.

Abstract

N-Methyl-d-aspartate (NMDA) receptors exhibit a dichotomy of signaling with both toxic and plastic responses. Recent reports have shown that exposure to subtoxic concentration of NMDA results in a neuroprotective state that was measured when these neurons were subsequently challenged with toxic doses of glutamate or kainate. Control of polysialylated neural cell adhesion molecule (PSA-NCAM) expression by NMDA receptor activation has been described in several systems, suggesting a functional link between these two proteins. The perception of glial role in CNS function has changed dramatically over the past few years from simple trophic functions to that of cells with important roles in development and maintenance of CNS in cooperation with neurons. We report here the transcriptional regulation of PSA-NCAM expression by subtoxic dose of NMDA in retinoic acid differentiated C6 glioma cell cultures. C6 glioma cell cultures differentiated with retinoic acid (10microM) were exposed to NMDA (100microM) or to antagonist MK-801 (200nM) prior to treatment with NMDA and cells were harvested after 24h of treatment to study the expression of total NCAM, PSA-NCAM, nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1) by Western blotting and dual immunocytofluorescence and expression of PST mRNA by fluorescent in situ hybridization (FISH). Significant increase in the levels of PSA-NCAM, NF-kappaB, AP-1 and PST mRNA was observed in NMDA treated cultures. Treatment of cultures with MK-801, a non-competitive NMDA receptor antagonist, prior to NMDA exposure prevented the NMDA-mediated changes indicating the involvement of NMDA receptor activation. The results elucidate the possible cellular and molecular mechanisms of regulation of PSA-NCAM expression in astroglial cultures by extracellular signals.

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Transcriptional regulation of PSA-NCAM expression by NMDA receptor activation in RA-differentiated C6 glioma cultures - PubMed (original) (raw)