DNA hypomethylating agents 5-aza-2'-deoxycytidine and valproate increase neuronal 5-lipoxygenase mRNA.
DNA methylation regulates gene expression. Neuronal 5-lipoxygenase expression increases during aging and during the proliferation of immature rat cerebellar granule neurons. In these cultures, we investigated the effects of hypomethylating agents 5-aza-2'-deoxycytidine (AdC) and valproate on 5-lipoxygenase mRNA. Both drugs increased 5-lipoxygenase mRNA in proliferating cells; only valproate was effective in differentiated neurons. We propose that neuronal 5-lipoxygenase expression can be affected by aging-altered DNA methylation and by hypomethylating drugs, such as the anticonvulsant valproate.
Manev
Hari
H
Department of Psychiatry, The Psychiatric Institute, University of Illinois at Chicago, Chicago, IL 60612, USA. HManev@psych.uic.edu
Uz
Tolga
T
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002478:Cells, Cultured; D002531:Cerebellum; D019175:DNA Methylation / Q000187:drug effects*; D000077209:Decitabine; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D014635:Valproic Acid / Q000494:pharmacology*
D012333:RNA, Messenger; D014635:Valproic Acid; D000077209:Decitabine; D001094:Arachidonate 5-Lipoxygenase; D001374:Azacitidine