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Journal of Biochemistry Advance Access published online on November 14, 2008
Journal of Biochemistry, doi:10.1093/jb/mvn152
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© The authors 2008. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Prostaglandin F2{alpha} synthase activities of aldo-keto reductase 1B1, 1B3 and 1B7

Zakayi Kabututu1, Michèle Manin2, Jean-Christophe Pointud2, Toshihiko Maruyama1, Nanae Nagata1, Sarah Lambert2, Anne-Marie Lefrançois-Martinez2, Antoine Martinez2 and Yoshihiro Urade1

1Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan
2CNRS, UMR6247 - Genetic, Reproduction & Development (GReD); Clermont University; 24 avenue des Landais, 63177 Aubière, France

To whom correspondence should be addressed. Y. Urade, Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan. Tel. +81-6-6872-4851. Fax: +81-6-6872-2841. E-mail: uradey{at}obi.or.jp

Received September 4, 2008; Accepted October 30, 2008


  Abstract

Here we show that 3 enzymes belonging to the 1B group of the aldo-keto reductase (AKR) superfamily, i.e., human placental aldose reductase (AKR1B1), mouse kidney aldose reductase (AKR1B3), and mouse vas deferens protein (AKR1B7), catalyze the reduction of prostaglandin (PG) H2, a common intermediate of various prostanoids, to form PGF2{alpha}, in the presence of NADPH. AKR1B1, AKR1B3, and AKR1B7 displayed higher affinities for PGH2 (Km = 1.9, 9.3, and 3.8 µM, respectively) and Vmax values (26, 53, and 44 nmol/min/mg protein, respectively) than did the human lung PGF2{alpha} synthase (AKR1C3; 18 µM and 4 nmol/min/mg protein, respectively). The PGF2{alpha} synthase activity of AKR1B1 and AKR1B3 was efficiently inhibited by 2 AKR inhibitors, tolrestat (Ki = 3.6 and 0.26 µM, respectively) and sorbinil (Ki = 21.7 and 0.89 µM, respectively), in a non-competitive or mixed-type manner, whereas that of AKR1B7 was not sensitive to these inhibitors (Ki = 9.2 and 18 mM, respectively). These data provide a molecular basis for investigating novel functional roles for AKR1B members and PGF2{alpha} as mediators of physiological and pathological processes in mammalian organisms.

Key Words: prostaglandin F2{alpha}, prostaglandin H2, prostaglandin H2 F2{alpha}-reductase, tolrestat, sorbinil


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