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evolution
most prostaglandin F2alpha synthases (PGFS) identified to date are aldo-ketoreductases, AKRs
evolution
the enzyme belongs to the aldo-keto reductase family 1
malfunction
administration of an AKR1C3 inhibitor significantly decreases 11beta-PGF2alpha concentrations in culture media of breast cancer cells
malfunction
although attenuating AKR1C3 expression in squamous cell carcinoma cells by siRNA does not affect growth, treatment with PGD2 and its dehydration metabolite, 15delta-PGJ2, decreases squamous cell carcinoma, SCC, proliferation in a PPARgamma-dependent manner. In addition, treatment with the PPARgamma agonist pioglitazone profoundly inhibits squamous cell carcinoma proliferation. SCC-AKR1C3 metabolizes protaglandin D2, PGD2, to 9alpha,11beta-prostaglandin F2 12fold faster than the parent cell line and is protected from the antiproliferative effect mediated by PGD2. PGD2 and its metabolite 15delta-prostaglandin J2 attenuate SCC proliferation in a PPARgamma-dependent manner, therefore activation of PPARgamma by agonists such as pioglitazone may benefit those at high risk of SCC
malfunction
the enzyme inhibitor 15-deoxy-delta12,14-prostaglandin J2 attenuates proliferation, inhibits collagen gel contraction and induces activation of the apoptotic marker, caspase-3, in CRL1762 keloid fibroblasts, overview
metabolism
AKR1B1 is able to produce PGF2alpha in the endometrium in addition toAKR1C3. The PGF synthase activity of AKR1B1 proves to be much higher than that of AKR1C3
metabolism
AKR1B1 is involved in the synthesis of PGF2alpha. Pathways of prostaglandin F2alpha biosynthesis in human cells, overview
metabolism
AKR1C3 is able to produce PGF2alpha in the endometrium in addition to AKR1B1. The PGF synthase activity of AKR1B1 proves to be much higher than that of AKR1C3
metabolism
AKR1C3 is an enzyme responsible for the metabolism of steroid hormones such as androgens, progesterones and estrogens in addition to the reduction of PGD2 to 11beta-PGF2alpha
metabolism
availability of prostaglandins can be regulated by changes in 15-hydroxyprostaglandin dehydrogenase, HPGD, an enzyme that catabolizes prostaglandin E2 and prostaglandin F2alpha to their inactive metabolites 13,14-dihydro-15keto-PGF2alpha and 13,14-dihydro-15-keto prostaglandin E2 (PGEM)
metabolism
enzyme PGF is involved in essential lipid metabolism pathways
metabolism
enzyme PGF is involved in essential lipid metabolism pathways
metabolism
the prostaglandin H2 (PGH2) is the common precursor of prostaglandin F2alpha (PGF2alphha) and prostaglandin E2 (PGE2). PGH2 is converted into one of the active prostaglandins by a specific terminal synthase, such as PGE2 synthase (PGES), which is responsible for PGE2 production or 9,11-endoperoxidase reductase, which has PGF2alpha synthase (PGFS) activity
metabolism
there are three different pathways for the synthesis of the uterotonic PGF2alpha: 1. from PGH2 by PGH 9-,11-endoperoxide reductase, 2. from PGD2 by PGD 11-ketoreductase, 3. from PGE2 by PGE 9-ketoreductase
metabolism
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enzyme PGF is involved in essential lipid metabolism pathways
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physiological function
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prostamide/PGF synthase may play an important functional role in the central nervous system
physiological function
prostamide/PGF synthase may play an important functional role in the central nervous system. It directly synthesizes prostamide/PGF2alpha from prostamide/PGH2 better than PGF synthase
physiological function
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knock-down by small interfering RNA for Akr1b3 suppresses PGF2 production and enhances the expression of adipogenic genes such as peroxisome proliferator-activated receptor gamma, fatty acid-binding protein 4, and stearoyl-CoA desaturase
physiological function
AKR1C3 is overexpressed in skin squamous cell carcinoma (SCC) and affects SCC growth via prostaglandin metabolism. AKR1C3 is overexpressed in various malignancies, suggesting a tumor promoting function. SCC-AKR1C3 metabolizes protaglandin D2, PGD2, to 9alpha,11beta prostaglandin F2. Unlike other AKR1C members, AKR1C3 can synthesize prostaglandin F2alpha from prostaglandin H2, an arachidonic acid derivative synthesized by cyclooxygenase
physiological function
in breast cancer, the status of the 11alpha-PGF2alpha and 11beta-PGF2alpha cognate FP receptor is associated with adverse clinical outcome only in the AKR1C3 positive cases, immunohistochemical analysis. FP receptor-mediated functions of 11beta-PGF2alpha using FP receptor expressed MCF-7 cell line shows that 11beta-PGF2alpha treatment phosphorylates ERK and CREB and induces Slug expression through FP receptor in MCF-FP, and MCF-FP cells demonstrate decreased chemosensitivity compared to parental controls. The actions of AKR1C3, but not of AKR1B1, can produce FP receptor ligands whose activation results in carcinoma cell survival in breast cancer. 11beta-PGF2alpha stimulates phosphorylation of ERK and CREB via FP receptor. AKR1C3-dependent signaling performs through 11beta-PGF2alpha and the FP receptor, overview
physiological function
in breast cancer, the status of the 11alpha-PGF2alpha and 11beta-PGF2alpha cognate FP receptor is associated with adverse clinical outcome only in the AKR1C3 positive cases, while there are no significant correlations between FP receptor status and any of the clinicathological parameters in AKR1B1 positive cases. AKR1B1 does not induce Slug expression
physiological function
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lentiviral vector-mediated delivery of the prostaglandin F synthase (PGFS) gene resultes in long-term reduction of intraocular pressure and may eliminate off-target tissue effects and the need for daily topical PGF2alpha self-administration
physiological function
PGF2alpha plays important roles in the regulation of ocular pressure, renal absorption, cardiovascular function, adipocyte differentiation, and female reproductive function. Role of AKR1C3 in the formation of PGF2alpha from PGH2 in the bovine endometrium
physiological function
PGF2alpha plays important roles in the regulation of ocular pressure, renal absorption, cardiovascular function, adipocyte differentiation, and female reproductive function. Role of bovine AKR1B1, previously known as AKR1B5, in the formation of PGF2alpha from PGH2 in the bovine endometrium
physiological function
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prostaglandin F2alpha is the main luteolytic factor in pigs and its biosynthesis is catalyzed by prostaglandin F2alpha synthase, PGFS. The enzyme acts via specific seven-transmembrane G protein-coupled receptor (PTGFR) localized in large luteal cells. Intraluteal action of PGF2alpha causes a decrease in steroidogenic capacity and diminished production of progesterone. Intraluteal production of PGF2a is considered to be an important part of the luteolytic machinery
physiological function
prostaglandins (PGs) are important regulators of female reproductive function. The primary PGs produced in the endometrium are PGE2 and PGF2alpha. Role of aldo-ketoreductase (AKR)1B1 in increased PGF2alpha production by human endometrial cells following stimulation with interleukin-1beta (IL-1beta)
physiological function
the enzyme is involved in prostaglandins metabolism. The produced PGF2alpha can not only promote prostate cancer cell's proliferation but also enhance prostate cancer cells resistance to radition. Overexpression of AKR1C3 significantly enhances human prostate cancer cells PCa resistance to radiation (or tert-butyl hydroperoxide) through activation of MAPK pathway. AKR1C3 has a pivotal role in the radioresistance of esophageal cancer and non-small-cell lung cancer
physiological function
The major eicosanoid secreted by mast cells is prostaglandin D2 (PGD2), a relatively unstable pro-inflammatory mediator which can be spontaneously converted to 15-deoxy-(Delta12,14)-prostaglandin J2(15d-PGJ2) or enzymatically metabolized to 9alpha,11beta-PGF2 by aldo-keto reductase 1C3 (AKR1C3). Role of enzyme AKR1C3-mediated prostaglandin D2 (PGD2) metabolism in keloids, overview. Keloids are progressively expanding scars, mostly prevalent in individuals of African descent. Metabolism of PGD2 to 9a,11b-PGF2 by both, keloids and normal fibroblasts, is dependent on AKR1C3
physiological function
the utero/placental expression of PGFS (AKR1C3) is identified in the superficial uterine glands throughout gestation and in the trophoblast cells within the feto-maternal contact zone during placentation, suggesting a possible role for PGFS (AKR1C3) in the trophoblast invasion
physiological function
overexpression of PGF2S leads to an increase of infectivity in vitro
physiological function
parasites overexpressing PGFS show alteration of enzymes associated with oxidative stress protection such as superoxide dismutase A and trypanothione reductase. Transfected parasites are approximately 2 times more susceptible to benznidazole and 10 times more susceptible to H2O2, and to genetic damage and oxidative stress. Transfected parasites are less infective than wild-type parasites and they show higher alteration in mitochondrial membrane potential and cell cycle after treatment with benznidazole
physiological function
PGFS overexpressing parasites are less able to complete the infective cycle in cell culture infections and increase cardiac tissue parasitic load in infected mice. Parasites overexpressing the enzyme increase PGF2alpha synthesis from arachidonic acid and display increased susceptibility to benznidazole and nifurtimox but increased resistance to hydrogen peroxide
physiological function
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overexpression of PGF2S leads to an increase of infectivity in vitro
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physiological function
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PGFS overexpressing parasites are less able to complete the infective cycle in cell culture infections and increase cardiac tissue parasitic load in infected mice. Parasites overexpressing the enzyme increase PGF2alpha synthesis from arachidonic acid and display increased susceptibility to benznidazole and nifurtimox but increased resistance to hydrogen peroxide
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physiological function
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parasites overexpressing PGFS show alteration of enzymes associated with oxidative stress protection such as superoxide dismutase A and trypanothione reductase. Transfected parasites are approximately 2 times more susceptible to benznidazole and 10 times more susceptible to H2O2, and to genetic damage and oxidative stress. Transfected parasites are less infective than wild-type parasites and they show higher alteration in mitochondrial membrane potential and cell cycle after treatment with benznidazole
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physiological function
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prostaglandin F2alpha is the main luteolytic factor in pigs and its biosynthesis is catalyzed by prostaglandin F2alpha synthase, PGFS. The enzyme acts via specific seven-transmembrane G protein-coupled receptor (PTGFR) localized in large luteal cells. Intraluteal action of PGF2alpha causes a decrease in steroidogenic capacity and diminished production of progesterone. Intraluteal production of PGF2a is considered to be an important part of the luteolytic machinery
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additional information
a loop with residues 188-196 in TrcrA.00019.a.B1 shows significant movement between the apoenzyme and holoenzyme. The Trypanosoma cruzi loop becomes ordered and a key interaction with one of the phosphates of NADP at Ser193 is likely to stabilize this region
additional information
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a loop with residues 188-196 in TrcrA.00019.a.B1 shows significant movement between the apoenzyme and holoenzyme. The Trypanosoma cruzi loop becomes ordered and a key interaction with one of the phosphates of NADP at Ser193 is likely to stabilize this region
additional information
a loop with residues 201-205 (disordered) in LemaA.00019.a.B1 shows significant movement between the apoenzyme and holoenzyme. The Leishmania major loop becomes ordered and a key interaction with one of the phosphates of NADP at Gln202 is likely to stabilize this region
additional information
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a loop with residues 201-205 (disordered) in LemaA.00019.a.B1 shows significant movement between the apoenzyme and holoenzyme. The Leishmania major loop becomes ordered and a key interaction with one of the phosphates of NADP at Gln202 is likely to stabilize this region
additional information
comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
additional information
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comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
additional information
comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
additional information
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comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
additional information
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a loop with residues 188-196 in TrcrA.00019.a.B1 shows significant movement between the apoenzyme and holoenzyme. The Trypanosoma cruzi loop becomes ordered and a key interaction with one of the phosphates of NADP at Ser193 is likely to stabilize this region
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