Deletion of the gene encoding prostamide/prostaglandin F synthase reveals an important role in regulating intraocular pressure.

Prostamide/prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide F and prostaglandin F (PGF). The importance of this enzyme, relative to the aldo-keto reductase (AKR) series, in providing functional tissue prostamide F levels was determined by creating a line of PM/PGFS gene deleted mice. Deletion of the gene encoding PM/PGFS (Fam213b / Prxl2b) was accomplished by a two exon disruption.

A comprehensive immunohistochemistry of prostaglandins F2α and E2 synthetic enzymes in rat ovary and uterus around parturition.

A comprehensive immunohistochemistry with the isoform-distinguishable antibodies against prostaglandin (PG) F2α and PGE2 biosynthetic enzymes was undertaken to identify the cellular types and enzyme isoforms in rat ovary and uterus around parturition. In general ovarian and uterine cells showed positive immunoreactions for phospholipase A2 groups 4A and 6A, but not group 2A, and cyclooxygenase (COX)-1 rather than COX-2. Their immunoreactions for PGF2α synthase and PGE2 synthase were cell type-dependently variable.

Mast cell maturation is driven via a group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis.

Microenvironment-based alterations in phenotypes of mast cells influence the susceptibility to anaphylaxis, yet the mechanisms underlying proper maturation of mast cells toward an anaphylaxis-sensitive phenotype are incompletely understood. Here we report that PLA2G3, a mammalian homolog of anaphylactic bee venom phospholipase A2, regulates this process. PLA2G3 secreted from mast cells is coupled with fibroblastic lipocalin-type PGD2 synthase (L-PGDS) to provide PGD2, which facilitates mast-cell maturation via PGD2 receptor DP1.

Recent reports about enzymes related to the synthesis of prostaglandin (PG) F(2) (PGF(2α) and 9α, 11β-PGF(2)).

Prostaglandin (PG) F(2α) is widely distributed in various organs and exhibits various biological functions, such as luteolysis, parturition, aqueous humor homeostasis, vasoconstriction, rennin secretion, pulmonary fibrosis and so on. The first enzyme reported to synthesize PGF(2) was referred to as PGF synthase belonging to the aldo-keto reductase (AKR) 1C family, and later PGF(2α) synthases were isolated from protozoans and designated as members of the AKR5A family. In 2003, AKR1B5, which is highly expressed in bovine endometrium, was reported to have PGF(2α) synthase activity, and recently, the paper entitled 'Prostaglandin F(2α) synthase activities of AKR 1B1, 1B3 and 1B7' was reported by Kabututu et al.

Preferential localization of prostamide/prostaglandin F synthase in myelin sheaths of the central nervous system.

Prostaglandin (PG) F(₂α) is a product of cyclooxygenase (COX)-catalyzed metabolism of arachidonic acid and exerts biological functions in various tissues. Prostaglandin ethanolamide (prostamide) F(₂α) is a COX-2-catalyzed metabolite of arachidonoyl ethanolamide (anandamide) that induces pharmacological actions in ocular tissues. Although PGF(₂α) is one of the most abundant prostaglandins in the brain, function of PGF(₂α) in the central nervous system (CNS) has not been extensively investigated.

Regulation of prostaglandin biosynthesis by interleukin-1 in cultured bovine endometrial cells.

Interleukin-1 (IL1) has been shown to be a potent stimulator of prostaglandin (PG) production in bovine endometrium. The aim of the present study was to determine the cell types in the endometrium (epithelial or stromal cells) responsible for the secretion of PGE2 and PGF2alpha in response to IL1A, and the intracellular mechanisms of IL1A action. Cultured bovine epithelial and stromal cells were exposed to IL1A or IL1B (0.

Two pathways for prostaglandin F2 alpha synthesis by the primate periovulatory follicle.

Prostaglandin E2 (PGE2) has been identified as a PG necessary for ovulation, but the ovulatory gonadotropin surge also increases PGF2 alpha levels in primate periovulatory follicles. To better understand the role of PGF2 alpha in ovulation, pathways utilized for PGF2 alpha synthesis by the primate follicle were examined. Monkeys were treated with gonadotropins to stimulate multiple follicular development; follicular aspirates and whole ovaries were removed before and at specific times after administration of an ovulatory dose of hCG to span the 40 h periovulatory interval.

Recruitment of thioredoxin-like domains into prostaglandin synthases.

A variety of prostaglandin (PG) synthases with different evolutionary origins have been identified. These enzymes catalyze reduction and oxidation reactions. However, despite the similarity in their reactions, thioredoxin-like proteins were not found in the PG synthesis pathway until recently.

Studies on membrane-associated prostaglandin E synthase-2 with reference to production of 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT).

Membrane-associated prostaglandin (PG) E synthase (mPGE synthase)-2 catalyzes the conversion of PGH(2) primarily to PGE(2). The enzyme is activated by various sulfhydryl reagents including dithiothreitol, dihydrolipoic acid, and glutathione, and it is different from mPGE synthase-1 and cytosolic PGE synthase, both of which require specifically glutathione. Recently, other investigators reported that their preparation of mPGE synthase-2 containing heme converted PGH(2) to 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) rather than to PGE(2) [T.

Prostaglandin E2 induces hypertrophic changes and suppresses alpha-skeletal actin gene expression in rat cardiomyocytes.

Prostaglandin E2 (PGE2) is a potent lipid mediator in a diverse range of biological processes. This study examined the hypertrophic effect of PGE2 in primary cultured rat neonatal cardiomyocytes. PGE2 increased total protein synthesis in a dose-dependent manner, as measured by [3H]-phenylalanine uptake.

Molecular characterization of a novel type of prostamide/prostaglandin F synthase, belonging to the thioredoxin-like superfamily.

Prostaglandin F (PGF) ethanolamide (prostamide F) synthase, which catalyzed the reduction of prostamide H(2) to prostamide F(2alpha), was found in mouse and swine brain. The enzyme was purified from swine brain, and its amino acid sequence was defined. The mouse enzyme consisted of a 603-bp open reading frame coding for a 201-amino acid polypeptide with a molecular weight of 21,669.

Prostaglandin F2alpha formation from prostaglandin H2 by prostaglandin F synthase (PGFS): crystal structure of PGFS containing bimatoprost.

Prostaglandin H(2) (PGH(2)) formed from arachidonic acid is an unstable intermediate and is efficiently converted into more stable arachidonate metabolites by the action of enzymes. Prostaglandin F synthase (PGFS) has dual catalytic activities: formation of PGF(2)(alpha) from PGH(2) by the PGH(2) 9,11-endoperoxide reductase activity and 9alpha,11beta-PGF(2) (PGF(2)(alphabeta)) from PGD(2) by the PGD(2) 11-ketoreductase activity in the presence of NADPH. Bimatoprost (BMP), which is a highly effective ocular hypotensive agent, is a PGF(2)(alpha) analogue that inhibits both the PGD(2) 11-ketoreductase and PGH(2) 9,11-endoperoxide reductase activities of PGFS.

Accumulation of S-2-hydroxyethyl derivatives of L-cysteine and L-homocysteine by a methionine auxotroph of Escherichia coli with the addition of 2-mercaptoethanol to the culture.

We previously reported [J. Biosci. Bioeng.

Molecular cloning and spatiotemporal expression of prostaglandin F synthase and microsomal prostaglandin E synthase-1 in porcine endometrium.

Endometrial prostaglandins (PGs) and the PGE2/PGF2alpha ratio play an important role in regulating the estrous cycle and establishment of pregnancy. The enzymes downstream of cyclooxygenase-2 may determine the PGE2/PGF2alpha ratio in the porcine uterus. Thus, we have cloned porcine PGF synthase (PGFS) and microsomal PGE synthase-1 (mPGES-1) and characterized their expression in porcine endometrium during the estrous cycle and early pregnancy.

Localization of cyclooxygenases-1 and -2, and prostaglandin F synthase in human kidney and renal cell carcinoma.

Prostaglandin (PG)F2alpha is one of the major prostanoids produced by the kidney, and its renal synthesis is regulated by sodium depletion, potassium depletion, and adrenal steroids. PGF synthase activity is detected in kidney of various mammals. Herein, we demonstrated immunochemically that PGF synthase was localized in proximal tubule of human kidney, together with cyclooxygenase (COX)-1, and that it was localized in human renal cell carcinoma, together with COX-2.

Crystal structure and possible catalytic mechanism of microsomal prostaglandin E synthase type 2 (mPGES-2).

Prostaglandin (PG) H(2) (PGH(2)), formed from arachidonic acid, is an unstable intermediate and is converted efficiently into more stable arachidonate metabolites (PGD(2), PGE(2), and PGF(2)) by the action of three groups of enzymes. Prostaglandin E synthase catalyzes an isomerization reaction, PGH(2) to PGE(2). Microsomal prostaglandin E synthase type-2 (mPGES-2) has been crystallized with an anti-inflammatory drug indomethacin (IMN), and the complex structure has been determined at 2.

Membrane-associated prostaglandin E synthase-1 is required for neuropathic pain.

It is widely accepted that prostaglandin (PG) E2 is the principal pro-inflammatory prostanoid and plays an important role in inflammatory pain. However whether PGE2 is involved in neuropathic pain remains unknown. PGE2 is produced from arachidonic acid via PGH2 by at least three PGE synthases (PGES), cytosolic PGES (cPGES), and membrane-associated PGES (mPGES)-1 and -2.

Synthesis of prostaglandin F ethanolamide by prostaglandin F synthase and identification of Bimatoprost as a potent inhibitor of the enzyme: new enzyme assay method using LC/ESI/MS.

Prostaglandin (PG) D(2) ethanolamide (prostamide D(2)) was reduced to 9alpha,11beta-PGF(2) ethanolamide (9alpha,11beta-prostamide F(2)) by PGF synthase, which also catalyzes the reduction of PGH(2) and PGD(2) to PGF(2alpha) and 9alpha,11beta-PGF(2), respectively. These enzyme activities were measured by a new method, the liquid chromatographic-electrospray ionization-mass spectrometry (LC/ESI/MS) technique, which could simultaneously detect the substrate and all products. PGF(2alpha), 9alpha,11beta-PGF(2), PGD(2), PGH(2), 9alpha,11beta-prostamide F(2), and prostamide D(2) were separated on a TSKgel ODS 80Ts column, ionized by electrospray, and detected in the negative mode.

Crystal structure of human prostaglandin F synthase (AKR1C3).

Prostaglandin H(2) (PGH(2)) formed from arachidonic acid is an unstable intermediate and is efficiently converted into more stable arachidonate metabolites (PGD(2), PGE(2), and PGF(2)) by the action of three groups of enzymes. Prostaglandin F synthase (PGFS) was first purified from bovine lung and catalyzes the formation of 9 alpha,11 beta-PGF(2) from PGD(2) and PGF(2)(alpha) from PGH(2) in the presence of NADPH. Human PGFS is 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) type II and has PGFS activity and 3 alpha-HSD activity.

Expression of key prostaglandin synthases in equine endometrium during late diestrus and early pregnancy.

Luteolysis in domestic species is mediated by the release of luteolytic pulses of prostaglandin (PG) F(2alpha) by the uterus at the end of diestrus, which must be suppressed by the conceptus to permit maternal recognition of pregnancy. In many species, including the horse, both the conceptus and the endometrium also synthesize PGE(2), which may antagonize PGF(2alpha) by playing a luteotropic and/or antiluteolytic role. While the release of PGE(2) and PGF(2alpha) by the equine endometrium in late diestrus and early pregnancy has been previously studied, the underlying prostaglandin synthase gene regulatory mechanisms remain poorly defined.

Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and -2.

Current evidence suggests that two forms of prostaglandin (PG) E synthase (PGES), cytosolic PGES and membrane-bound PGES (mPGES) -1, preferentially lie downstream of cyclooxygenase (COX) -1 and -2, respectively, in the PGE2 biosynthetic pathway. In this study, we examined the expression and functional aspects of the third PGES enzyme, mPGES-2, in mammalian cells and tissues. mPGES-2 was synthesized as a Golgi membrane-associated protein, and spontaneous cleavage of the N-terminal hydrophobic domain led to the formation of a truncated mature protein that was distributed in the cytosol with a trend to be enriched in the perinuclear region.

Essential 110Cys in active site of membrane-associated prostaglandin E synthase-2.

The amino acid sequence of membrane-associated prostaglandin (PG) E synthase-2 (mPGE synthase-2), which has a broad specificity in its thiol requirement for a catalytic activity, has the consensus region from 104Leu to 120Leu found in glutaredoxin and of thioredoxin. The sequence of Cys-x-x-Cys in the consensus region is the active site for thioredoxin and mPGE synthase-2 also has this amino acid sequence (110Cys-x-x-113Cys). The mutation from 110Cys to Ser or the double mutation from 110Cys and 113Cys to Ser caused loss of PGE synthase activity, whereas the single mutation from 113Cys to Ser did not affect the enzyme activity.