title: Evaluation of the prostaglandin F synthase activity of human and bovine aldo-keto reductases: AKR1A1s complement AKR1B1s as potent PGF synthases.
abstract: AKR1B1 of the polyol pathway was identified as a prostaglandin F2α synthase (PGFS). Using a genomic approach we have identified in the endometrium five bovine and three human AKRs with putative PGFS activity and generated the corresponding recombinant enzymes. The PGFS activity of the recombinant proteins was evaluated using a novel assay based on in situ generation of the precursor of PG biosynthesis PGH2. PGF2α was measured by ELISA and the relative potencies of the different enzymes were compared. We identified AKR1A1 and confirmed AKR1B1 as the most potent PGFS expressing characteristic inhibition patterns in presence of methylglyoxal, ponalrestat and glucose.
authors.affiliation: Centre de Recherche du CHU de Québec (CHUL), Département d'Obstétrique et Gynécologie, Axe de reproduction, santé de la mère et de l'enfant, Université Laval, Ste-Foy, Québec, Canada GIV 4G2.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lacroix Pépin
authors.forename: Pierre
authors.initials: P
authors.lastname: Chapdelaine
authors.forename: Michel A
authors.initials: MA
authors.lastname: Fortier
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D015237:Dinoprost / Q000096:biosynthesis; D004717:Endometrium / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D004791:Enzyme Inhibitors; D015237:Dinoprost; D006911:Hydroxyprostaglandin Dehydrogenases; C031051:prostaglandin-F synthase; C580929:AKR1A1 protein, human; C484670:AKR1B1 protein, human; D000449:Aldehyde Reductase
keywords: AA; AKR; AKR1A1; AKR1B1; AKR1C; Aldose reductase; BLOTTO; COX; DD3; Endometrium; IL-1β; PBS with Tween 20; PBS-T; PGD2; PGE2; PGF2α; PGF2α synthase; PGFS; PGG2; PGH2; PGs; aldo-keto reductases; arachidonic acid; cyclooxygenase; dihydrodiol dehydrogenase 3; fat-free dry milk in PBS-T; interleukine-1 beta; prostaglandin D2; prostaglandin E2; prostaglandin F2α; prostaglandin G2; prostaglandin H2; prostaglandins