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.

Key Words::

• Aldehyde oxidase
• rat strain difference
• native-PAGE
• western blot

Acknowledgements

We thank to Dr T. Ikeda, Director of the Drug Metabolism and Pharmacokinetics Research Laboratories, Sankyo Co. Ltd, and Drs K. Nishimura and Y. Kawahara, Ex-directors of the Research Laboratories, for their kind encouragement.