Clinically relevant concentrations of valproic acid modulate melatonin MT(1) receptor, HDAC and MeCP2 mRNA expression in C6 glioma cells.
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.
Kim
Bora
B
Department of Psychiatry and Behavioural Neurosciences, McMaster University, HSC-4N77, Hamilton, ON, Canada.
Rincón Castro
Lyda M
LM
Jawed
Sana
S
Niles
Lennard P
LP
D000818:Animals; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma / Q000201:enzymology / Q000235:genetics*; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D044122:Receptor, Melatonin, MT1 / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology*; D000099186:Histone Deacetylase 3
D004791:Enzyme Inhibitors; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D051783:Methyl-CpG-Binding Protein 2; D012333:RNA, Messenger; D044122:Receptor, Melatonin, MT1; D012097:Repressor Proteins; D014635:Valproic Acid; D000099186:Histone Deacetylase 3; C497394:Mecp2 protein, rat; C012589:trichostatin A; C515890:Hdac1 protein, rat; C533426:Hdac2 protein, rat