title: Glutathione-S-transferase expression in the brain: possible role in ethanol preference and longevity.
abstract: Identification of genes that are differentially expressed in rats bidirectionally selected for alcohol preference might reveal biological mechanisms underlying alcoholism or related phenotypes. Microarray analysis from medial prefrontal cortex (mPFC), a key brain region for drug reward, indicated increased expression of glutathione-S-transferases of the alpha (Gsta4) and mu (Gstm1-5) classes in ethanol-preferring AA rats compared with nonpreferring ANA rats. Real-time RT polymerase chain reaction (RT-PCR) analysis demonstrated approximately 2-fold higher Gsta4 transcript levels in several brain regions of ethanol-naive AA compared with ANA rats. Differences in mRNA levels were accompanied by differential levels of GSTA4 protein. We identified a novel haplotype variant in the rat Gsta4 gene, defined here as var3. Allele frequencies of var3 were markedly different between AA and ANA rats, 52% and 100%, respectively. Gsta4 expression was strongly correlated with the gene dose of var3, with approximately 60% of the variance in expression accounted for by genotype at this locus. The contribution of glutathione S-transferase expression to the ethanol-preferring phenotype is presently unclear. It could, however, underlie observed differences in life span between AA and ANA lines, prompting a utility of this animal model in aging research.
authors.affiliation: Laboratory of Clinical and Translational Studies, NCI, National Institutes of Health, Bethesda, USA.
authors.forename: K
authors.initials: K
authors.lastname: Björk
authors.forename: S T
authors.initials: ST
authors.lastname: Saarikoski
authors.forename: C
authors.initials: C
authors.lastname: Arlinde
authors.forename: L
authors.initials: L
authors.lastname: Kovanen
authors.forename: D
authors.initials: D
authors.lastname: Osei-Hyiaman
authors.forename: M
authors.initials: M
authors.lastname: Ubaldi
authors.forename: M
authors.initials: M
authors.lastname: Reimers
authors.forename: P
authors.initials: P
authors.lastname: Hyytiä
authors.forename: M
authors.initials: M
authors.lastname: Heilig
authors.forename: W H
authors.initials: WH
authors.lastname: Sommer
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005091:Exons; D005787:Gene Frequency; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D008136:Longevity; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D017397:Prefrontal Cortex / Q000201:enzymology* / Q000254:growth & development; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D005982:Glutathione Transferase