Prostaglandin F2alpha synthase activities of aldo-keto reductase 1B1, 1B3 and 1B7.
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.
Kabututu
Zakayi
Z
Department of Molecular Behavioral Biology, Osaka Bioscience Institute, 6-2-4 Furuedai, Suita, Osaka 565-0874, Japan.
Manin
Michèle
M
Pointud
Jean-Christophe
JC
Maruyama
Toshihiko
T
Nagata
Nanae
N
Lambert
Sarah
S
Lefrançois-Martinez
Anne-Marie
AM
Martinez
Antoine
A
Urade
Yoshihiro
Y
D000449:Aldehyde Reductase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002384:Catalysis; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D044262:Prostaglandin H2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D011994:Recombinant Proteins; D044262:Prostaglandin H2; D006911:Hydroxyprostaglandin Dehydrogenases; C031051:prostaglandin-F synthase; C066498:Akr1b7 protein, mouse; D000449:Aldehyde Reductase