title: Lack of dimer formation ability in rat strains with low aldehyde oxidase activity.
abstract: Aldehyde oxidase (AO) is a homodimer with a molecular weight of 300 kDa. To clarify the reasons for the well-known differences in rat strains, we set out to study the relationship between AO activity and the expression levels of its dimer. AO-catalyzed 2-oxidation activity of (S)-RS-8359 was measured in liver cytosols from ten rat strains. The expression levels of AO dimeric protein were evaluated by the native-PAGE/Western blot. Rat strains with low AO activity showed only a monomer, whereas strains with high activity overwhelmingly exhibited a dimer. Exceptionally, one strain in the high AO activity group displayed complex mixed expression patterns of low and high AO activity groups. However, there was a good relationship between AO activity and the expression levels of a dimer, but not of a monomer. The results suggest that rat strains with low AO activity lack the ability to produce a dimer necessary for catalytic activity, and AO differences in rat strains should be discussed in terms of the expression levels of the dimer itself.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, Tohoku Pharmaceutical University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: H
authors.initials: H
authors.lastname: Maruyama
authors.forename: M
authors.initials: M
authors.lastname: Adachi
authors.forename: K
authors.initials: K
authors.lastname: Hoshino
authors.forename: N
authors.initials: N
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
mesh_terms: D042931:Aldehyde Oxidase / Q000737:chemistry* / Q000502:physiology*; D000818:Animals; D019281:Dimerization; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
chemical_list: D042931:Aldehyde Oxidase