Disease relevance of PTGES2

• In conclusion, mPGES-1, cPGES, and mPGES-2 are all expressed in gastric ulcer tissue, but only mPGES-1 parallels COX-2 expression in mesenchymal and inflammatory cells of the ulcer bed, suggesting a key role for this enzyme in the ulcer repair process [1].
• Microsomal prostaglandin E synthase (mPGES)-1, mPGES-2 and cytosolic PGES expression in human gastritis and gastric ulcer tissue [1].
• Human granulosa-lutein cells obtained from women undergoing treatment for infertility expressed mRNAs for mPGES-1, mPGES-2 and cPGES [2].
• Interestingly, a considerable elevation of mPGES-2 expression was observed in human colorectal cancer [3].

High impact information on PTGES2

• IFN-gamma-activated transcriptional element (GATE)-binding factor 1 (GBF1) was identified as a transactivator that induces gene expression through GATE, a novel IFN-inducible element [4].
• Cellular prostaglandin E2 production by membrane-bound prostaglandin E synthase-2 via both cyclooxygenases-1 and -2 [3].
• Crystal structure and possible catalytic mechanism of microsomal prostaglandin E synthase type 2 (mPGES-2) [5].
• The geometry suggests that the S(gamma) of C110 is most likely the catalytic site of mPGES-2 [5].
• The fold of mPGES-2 is quite similar to those of GSH-dependent hematopoietic prostaglandin D synthase, except for the two large loop sections [5].

Biological context of PTGES2

• Essential 110Cys in active site of membrane-associated prostaglandin E synthase-2 [6].
• These observations strongly suggest that the up-regulation of terminal PGESs that are preferentially coupled with COX-1, especially mPGES-2, plays the pivotal role in PS liposome-induced PGE2 production by microglia [7].
• We also show GBF1 interacts with CAAAT/enhancer binding protein-beta (C/EBP-beta), the other GATE binding factor [8].
• The present study was undertaken to clone these enzymes and to study their tissue distribution, along with mPGES-2 [9].

Anatomical context of PTGES2

• We show mPGES-1 protein located predominantly in myometrial and vascular smooth muscle cells (SMCs), whilst mPGES-2 protein is largely in stromal cells surrounding the SMC and cPGES is diffusely located throughout the myometrium [10].
• Immunohistochemical analysis showed strong mPGES-1 expression in fibroblasts and macrophages of the ulcer bed, paralleling COX-2 expression. cPGES and mPGES-2 expression levels were seen in both fibroblasts of the ulcer bed and in epithelial cells [1].
• Monkey granulosa cells also expressed mPGES-2 and cPGES mRNA, but mRNA levels did not change in response to HCG administration [2].
• In contrast, mPGES-2 mRNA and protein were detected in all 10 cell lines [11].
• By Northern blot analysis, we found that mPGES-2 and cPGES mRNA were expressed in the endometrium, myometrium, ovary and oviduct, albeit at different levels, while mPGES-1 mRNA was detected at a weak level, mainly in the oviduct [9].

Associations of PTGES2 with chemical compounds

• 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 2.6A resolution. mPGES-2 forms a dimer and is attached to lipid membrane by anchoring the N-terminal section [5].
• Compounds 23 and 30 inhibit mPGES-1 with potencies in the low nanomolar range and with selectivities of at least 100-fold compared to their inhibition of mPGES-2, thromboxane synthase and binding affinity to FLAP [12].

Other interactions of PTGES2

• Prostaglandin E(2) (PGE(2)) is synthesized by one of three enzymes, cytosolic prostaglandin E synthase (cPGES), microsomal PGES-1 (mPGES-1) and microsomal PGES-2 (mPGES-2) [10].

Analytical, diagnostic and therapeutic context of PTGES2

• Western blot analysis showed mPGES-1 protein expression limited to open ulcer tissue, while mPGES-2 and cPGES immunoreactivities were seen in both open and closed ulcer tissue [1].
• On the other hand, mPGES-2 and cytosolic PGES (cPGES) that are functionally coupled with COX-1 were upregulated after treatment with PS liposomes or LPS [7].
• Recent gene targeting studies of mPGES-1 have revealed that this enzyme represents a novel target for anti-inflammatory and anti-cancer drugs. mPGES-2 is synthesized as a Golgi membrane-associated protein, and the proteolytic removal of the N-terminal hydrophobic domain leads to the formation of a mature cytosolic enzyme [13].

References