Disease relevance of PTGES

• We investigated the expression of PGES isoenzyme in articular chondrocytes from patients with osteoarthritis (OA) [1].
• Microsomal prostaglandin E synthase (mPGES)-1, mPGES-2 and cytosolic PGES expression in human gastritis and gastric ulcer tissue [2].
• Finally, tissue microarrays identified the same protein expression pattern for PGIS and PGES in 108 different non-small cell lung cancer biopsies, and the detection of PGIS had statistically significant prognostic value in patient survival [3].
• Recombinant p23 expressed in Escherichia coli and 293 cells exhibited all the features of PGES activity detected in rat brain cytosol [4].
• Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer [5].
• In vitro, hypoxia led to an enhanced synthesis of mPGES-1, coinciding with a nuclear accumulation of the transcription factor HIF-1alpha [6].

High impact information on PTGES

• Prostaglandin (PG) E(2) is formed from PGH(2) by a series of PGE synthase (PGES) enzymes [7].
• Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target [8].
• Membrane arachidonic acid is converted by cyclooxygenase (COX) into prostaglandin (PG) G(2) and then to PGH(2) which is subsequently metabolized to PGE(2) by PGE synthase (PGES) [9].
• Up-regulation of microsomal prostaglandin E synthase 1 in osteoarthritic human cartilage: critical roles of the ERK-1/2 and p38 signaling pathways [10].
• Expression of microsomal prostaglandin E synthase 1 in rheumatoid arthritis synovium [11].

Chemical compound and disease context of PTGES

• We suggest that in 2K1C, COX-1 and PGES expression may fail to oppose the effects of renovascular hypertension through reduced prostaglandin signaling in late distal tubule and cortical collecting duct [12].

Biological context of PTGES

• Prostaglandin E2 is an enhancer of interleukin-1beta-induced expression of membrane-associated prostaglandin E synthase in rheumatoid synovial fibroblasts [13].
• The induction of endothelial PGE-S and COX-2 appeared to be and their transcripts were induced as fast as one might expect from immediate early genes [14].
• Collectively, mPGES-2 is a unique PGES that can be coupled with both COXs and may play a role in the production of the PGE2 involved in both tissue homeostasis and disease [15].
• Microsomal PGES was also observed in cytotrophoblasts (CTs), but not in syncytiotrophoblasts (STs), in early gestation [16].
• Coordinate up- and down-regulation of glutathione-dependent prostaglandin E synthase and cyclooxygenase-2 in A549 cells. Inhibition by NS-398 and leukotriene C4 [17].

Anatomical context of PTGES

• Expression and regulation of prostaglandin E synthase isoforms in human myometrium with labour [18].
• Interleukin 1beta induces functional prostaglandin E synthase in cultured human umbilical vein endothelial cells [14].
• COX-2, PGES, and MMPs were especially noted in shoulders of symptomatic plaques, colocalizing with HLA-DR+ macrophages [19].
• GSH-dependent PGES activity in the cytosol of rat brains, but not of other tissues, increased 3-fold after lipopolysaccharide (LPS) challenge [4].
• Expression and localization of prostaglandin E synthase isoforms in human fetal membranes in term and preterm labor [20].

Associations of PTGES with chemical compounds

• IL-1beta-induced PGES activity, measured by conversion of PGH(2) to PGE(2), was decreased by rofecoxib [13].
• Actinomycin D, a classical transcription inhibitor, was used to prove that indeed IL-1beta induced the functional PGE-S enzyme [14].
• Cyclooxygenase-2 (COX-2) and PGE synthase (PGES) are coregulated in nucleated cells by inflammatory stimuli [19].
• Overexpression of functionally coupled cyclooxygenase-2 and prostaglandin E synthase in symptomatic atherosclerotic plaques as a basis of prostaglandin E(2)-dependent plaque instability [19].
• Conversion of PGH2 to PGE2 (PGES activity) was significantly increased in the lysate from IL-1beta-stimulated chondrocytes and it was inhibited by MK-886, which has an inhibitory effect on mPGES-1 activity [1].
• We found enhanced recruitment of ERalpha as well as the NFkappaB family member, p65, to the PTGES estrogen response element by the combination of E2 and TNFalpha compared with either E2 or TNFalpha alone [21].
• R126A and R126Q mPGES-1 exhibit a novel, glutathione-dependent, reductase activity, which allows conversion of prostaglandin H2 into prostaglandin F2alpha [22].

Regulatory relationships of PTGES

• This study examines the hypothesis that transforming growth factor beta (TGFbeta) regulates cyclooxygenase-2 (COX-2) and induces prostaglandin E synthase (mPGES-1) in rat mesangial cells [23].
• OT had no influence on the expression of PGES and PGFS [24].
• Nevertheless, PGES was expressed in SMCs and induced by IL-1beta and TNF-alpha, and by PMA and LPS, although to a lesser extent [25].

Other interactions of PTGES

• Prostaglandin E synthase (PGES), which isomerizes COX-derived PGH2 specifically to PGE2, occurs in multiple forms with distinct enzymatic properties, expressions, localizations and functions [26].
• Recently, a microsomal protein with 38% sequence identity to microsomal glutathione S-transferase 1 was shown to constitute an inducible, glutathione-dependent prostaglandin E synthase (PGES) [17].
• Recent studies have identified three PGE synthase (PGES) isozymes: cytosolic PGES (cPGES) and microsomal PGES (mPGES)-1 and -2, but little is known regarding the expression and roles of these enzymes in gastric fibroblasts [27].
• Flow cytometry on primary CVX and NCK and immunohistochemical staining of formalin fixed paraffin-embedded tumor specimens from which primary CVX cultures were derived as well as from a separate set of invasive cervical cancers confirmed differential expression of the CDKN2A/p16 and PTGES markers on CVX versus NCK [28].
• Finally, a comparison of the mGST-I and PIG12 sequences with those of FLAP, LTC4 synthase, mGST-II, and mGST-III suggests that these proteins are the related products of a dispersed microsomal GST gene superfamily [29].

Analytical, diagnostic and therapeutic context of PTGES

• Functional expression of PGE-S was measured at the level of specific mRNA by semi-quantitative RT-PCR, PGE-S protein was detected by Western blot in HUVEC, while PGE2 was measured by immunoassay in the supernatant [14].
• Chondrocytes were treated with various cytokines and the expression of PGES isoenzyme mRNA was analyzed by the reverse transcription-polymerase chain reaction and Northern blotting, whereas Western blotting was performed for protein expression [1].
• To investigate the relationship between cyclooxygenase and PGES, a time-course study on protein expression was performed in A549 cells after treatment with interleukin-1beta [17].
• Western blot analyses revealed a predominant protein band of 180 kDa, and a second 16-kDa band for ir-PGES and 56-kDa band for ir-PGIS [30].
• RESULTS: Both PGDS and PGES were detected in nasal polyps by immunohistochemistry [31].

References