Dimethyl fumarate regulates histone deacetylase expression in astrocytes

摘要: Abstract We previously showed that dimethyl fumarate (DMF) reduces inflammatory activation in astrocytes, involving of transcription factor Nrf2. However, the pathways causing Nrf2 were not examined. now show DMF modifies expression histone deacetylases (HDACs) primary rat astrocytes. After 4 h incubation, levels HDAC1, 2, and 4 mRNAs increased by DMF; however, after 24 h, returned to or below control values. At time, HDAC protein overall activity also reduced DMF. Stimulation astrocytes with pro-inflammatory cytokines significantly mRNA although at time point. In presence cytokines, mRNAs, proteins, activity. Proteomic analysis DMF-treated identified 8 proteins which lysine acetylation was DMF, including histones H2a.1 H3.3. A role for HDACs mediating actions is suggested findings selective inhibitor SAHA nuclear Nrf2:DNA binding activity, reversed a target gene heme-oxygenase 1. These data regulates astrocyte expression, could contribute activation, suppression responses cause long-lasting changes expression.