DNA Methyltransferase Inhibitors Induce Cerebral Dopamine Neurotrophic Factor Expression in C6 Glioma Cells

Cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived (MANF) are involved in neuroprotection mitigating endoplasmic reticulum (ER) stress the brain peripheral organs. In earlier work, an increase histone acetylation, following treatment with epigenetic modulator, valproic acid, was associated induction of CDNF MANF cultured cells rat brain. These findings prompted investigation effects DNA methyltransferase (DNMT) inhibitors, which can alter function, on expression MANF. Rat C6 glioma were treated a micromolar range DNMT inhibitors: 5-aza-2’-deoxycytidine (DAC or decitabine), 5-azacytidine (AZA) zebularine (ZEB) for 24 h. Subsequently, qPCR analysis used to examine mRNA DNMT1, ten-eleven translocation methylcytosine dioxygenase 2 (TET-2), A significant dose-dependent decrease DNMT1 levels, together TET-2 expression, observed AZA DAC. Importantly, DAC, ZEB caused levels. contrast, decreased AZA, no DAC ZEB. Western revealed changes protein levels The suggests that methylation is regulation this factor. Clarification other mechanisms underlying may provide novel therapeutic approaches neurodegenerative ER stress-related disorders.