title: Valproate administration to mice increases histone acetylation and 5-lipoxygenase content in the hippocampus.
abstract: Gene expression can be regulated by chromatin remodeling induced by the opposing actions of histone acetyltransferases and histone deacetylases (HDAC). HDAC inhibitors are considered putative anti-cancer drugs, but may also alter gene expression in the brain. Valproic acid (valproate; VPA), a drug used for treatment of bipolar disorder, has been characterized as a HDAC inhibitor. In neuronal cultures, VPA increases the expression of 5-lipoxygenase (5-LOX). Here we show that in vivo treatment of mice with intraperitoneal VPA injections increases the acetylation of histone H3 and the content of 5-LOX immunoreactive protein in the hippocampus. Since the extent of 5-LOX expression may alter mouse behavior, we suggest that VPA-altered chromatin remodeling and 5-LOX expression in the brain may be functionally important.
authors.affiliation: The Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Emre
authors.initials: E
authors.lastname: Yildirim
authors.forename: Zhijing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Tolga
authors.initials: T
authors.lastname: Uz
authors.forename: Chang-qing
authors.initials: CQ
authors.lastname: Chen
authors.forename: Radmila
authors.initials: R
authors.lastname: Manev
authors.forename: Hari
authors.initials: H
authors.lastname: Manev
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D014635:Valproic Acid; D001094:Arachidonate 5-Lipoxygenase