Lack of dimer formation ability in rat strains with low aldehyde oxidase activity.
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.
Itoh
K
K
Department of Drug Metabolism and Pharmacokinetics, Tohoku Pharmaceutical University, Japan.
Maruyama
H
H
Adachi
M
M
Hoshino
K
K
Watanabe
N
N
Tanaka
Y
Y
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
D042931:Aldehyde Oxidase