Clinically relevant concentrations of valproic acid modulate melatonin MT1 receptor, HDAC and MeCP2 mRNA expression in C6 glioma cells
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C6 glioma cells were treated with clinically relevant concentrations of valproic acid (0.5 or 1.0 mM) for 1-7 days and RT-PCR used to examine expression of the melatonin MT(1) receptor and selected epigenetic modulators. Valproic acid caused significant time-dependent changes in the mRNA expression of the melatonin MT(1) receptor, histone deacetylase (HDAC) 1, 2 and 3, and methyl CpG binding protein 2 (MeCP2). A structurally distinct HDAC inhibitor, trichostatin A, also caused a significant concentration-dependent induction of melatonin MT(1) receptor mRNA expression, suggesting involvement of an epigenetic mechanism. The ability of clinical concentrations of valproic acid to significantly alter melatonin MT(1) receptor expression, suggests a role for this receptor in the diverse neuropharmacological and oncostatic effects of this agent.
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