Prostaglandin F2 Synthase Activities of Aldo-Keto Reductase 1B1, 1B3 and 1B7
| Autor: | Nanae Nagata, Antoine Martinez, Toshihiko Maruyama, Zakayi Kabututu, Michèle Manin, Yoshihiro Urade, Sarah Lambert, Anne-Marie Lefrançois-Martinez, Jean-Christophe Pointud |
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| Rok vydání: | 2008 |
| Předmět: |
Tolrestat
medicine.medical_specialty Prostaglandin Reductase Biochemistry Catalysis Mice chemistry.chemical_compound Aldehyde Reductase Internal medicine medicine Animals Humans Molecular Biology chemistry.chemical_classification Aldo-keto reductase Aldose reductase ATP synthase biology General Medicine Recombinant Proteins Kinetics Endocrinology Enzyme chemistry Hydroxyprostaglandin Dehydrogenases biology.protein Prostaglandin H2 Sorbinil |
| Zdroj: | Journal of Biochemistry. 145:161-168 |
| ISSN: | 0021-924X |
| DOI: | 10.1093/jb/mvn152 |
| Popis: | Here, we show that three 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), catalyse the reduction of prostaglandin (PG) H(2), a common intermediate of various prostanoids, to form PGF(2alpha) in the presence of NADPH. AKR1B1, AKR1B3 and AKR1B7 displayed higher affinities for PGH(2) (K(m) = 1.9, 9.3 and 3.8 microM, respectively) and V(max) values (26, 53 and 44 nmol/min/mg protein, respectively) than did the human lung PGF(2alpha) synthase (AKR1C3; 18 microM and 4 nmol/min/mg protein, respectively). The PGF(2alpha) synthase activity of AKR1B1 and AKR1B3 was efficiently inhibited by two AKR inhibitors, tolrestat (K(i) = 3.6 and 0.26 microM, respectively) and sorbinil (K(i) = 21.7 and 0.89 microM, respectively), in a non-competitive or mixed-type manner, whereas that of AKR1B7 was not sensitive to these inhibitors (K(i) = 9.2 and 18 mM, respectively). These data provide a molecular basis for investigating novel functional roles for AKR1B members and PGF(2alpha) as mediators of physiological and pathological processes in mammalian organisms. |
| Databáze: | OpenAIRE |
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