PTGS2（也稱為COX-2）是一種關(guān)鍵的炎癥介質(zhì)，在炎癥反應(yīng)中發(fā)揮著重要作用。最新研究表明，PTGS2參與了許多疾病的發(fā)病機(jī)制，如腫瘤、炎癥性疾病、神經(jīng)系統(tǒng)疾病等。此外，PTGS2還與老年癡呆癥的發(fā)病有關(guān)。目前，許多抑制PTGS2的藥物正在研究和開(kāi)發(fā)中，以期能夠更好地治療相關(guān)疾病。

Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate, with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates arachidonate (AA, C20:4(n-6)) to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide PGH2, the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons. Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins. In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids. Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response. Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols. Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation. Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2. In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection. In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia.

1. Increased expression of COX-2 is associated with aortic endothelial dysfunction. PMID: 30292829
2. findings indicated that BMP9 is involved in the phosphate-induced calcification in VSMCs and COX-2 partly mediates the BMP9-induced calcification in VSMCs through activating Wnt/beta-catenin pathway. PMID: 29073723
3. the cortical COX2 pathway was activated in CUMS rats. Inhibition of COX2 activity/expression can obviously improve depressive behaviours in CUMS rats. Upregulating COX2 expression can increase the susceptibility of rats to CUMS. PMID: 28352129
4. The present study proposed that COX-2-mediated inflammation is important as a candidate target for hippocampal impairment in the hypothyroidism. PMID: 29436670
5. COX1 and 2 gene expression and localization in the injured brain regulating prostaglandin synthase. PMID: 28933223
6. In heart irradiation groups, 3-fold up-regulation of both ET-1 and COX-2 was observed. In pelvis irradiation groups, 3-fold up-regulation of ET-1 was seen, but not significant changes in COX-2 gene expression have observed at distant heart tissues after pelvis irradiation. PMID: 28508833
7. Microglial TNFalpha induces cyclooxygenase 2 (COX2) and PGI2 synthase expression in spinal endothelial cells during neuropathic pain. These findings further suggest that the glia-endothelial cell interaction of the neurovascular unit via transient TNFalpha is involved in the generation of neuropathic pain. PMID: 28451639
8. The authors measured brain oxygenation in localized areas from freely-moving rodents and discovered a severe hypoxic event (pO2 < 10 mmHg) after the termination of seizures. This event lasted over an hour, is mediated by hypoperfusion, generalizes to people with epilepsy, and is attenuated by inhibiting cyclooxygenase-2 or L-type calcium channels. PMID: 27874832
9. C2-ceramide enhances phenylephrine-induced vascular smooth muscle constriction by mediation of the ER stress/COX-2/PGE2 pathway. PMID: 28797762
10. Results point to an excess of reactive oxygen species mainly from NAD(P)H oxidase after aluminum exposure and increased vascular prostanoids from COX-2 acting in concert to decrease NO bioavailability, thus inducing vascular dysfunction and increasing blood pressure. PMID: 28826906
11. Hepatic COX2 expression and PGI2 production are enhanced in cirrhotic rats, but the correlation with Hepatic encephalopathy (HE) is not remarkable. PMID: 27580512
12. a stiffness-dependent YAP/TAZ-mediated positive feedback loop that drives remodeling phenotypes in pulmonary artery smooth muscle cells via reduced COX-2 and prostaglandin activity. PMID: 28642262
13. the disrupted pattern of hippocampal neurogenesis induced by MNU is different between developmental and postpubertal exposure and is dependant on COX2 regulation. PMID: 28688903
14. the long-lasting oligemia following cortical spreading depression consists of at least two distinct temporal phases, mediated by preferential actions of COX-1- and COX-2-derived prostanoids: an initial phase mediated by COX-1 that involves TXA2 followed by a later phase, mediated by COX-2 and PGF2alpha. PMID: 27178425
15. These data suggest that adaptive changes induced in the myocardium by CIH may include activation of cPLA2alpha and COX-2 via beta2-AR/Gi-mediated stimulation of the ERK/p38 pathway. PMID: 27686454
16. COX-2 protein expression was upregulated in lung tissue in response to skeletal muscle ischemia reperfusion PMID: 26724476
17. It was concluded that intestinal damage during acute pancreatitis is exacerbated in elderly rats compared with young rats and that COX-2 inhibition could be a potential therapeutic target to offer tailored treatment for acute pancreatitis in the elderly. PMID: 26610611
18. TNFalpha-RelB/p52 pathway may be involved in the early stages of renal damage, in part by stimulating COX-2 and inflammatory responses PMID: 26824492
19. COX1/2 inhibition alters the host response and reduces ECM scaffold mediated constructive tissue remodeling in a rodent model of skeletal muscle injury PMID: 26612417
20. Low-salt diet modulates mesenteric vascular responses via increased NO bioavailability suggested by increased iNOS protein expression and vasoconstrictor prostanoid production via COX-2. PMID: 26685759
21. These results suggest the existence of a causal link between Cox-2 and p53, which may represent a toxic mechanism of electrophilic lipid peroxidation products. PMID: 25506925
22. Src modulates the 4-Hydroxynonenal-enhanced activation of AP-1 and the expression of COX-2 PMID: 26466383
23. IL-1beta reduces tonic contraction of mesenteric lymphatic muscle cells, with the involvement of COX-2 and prostaglandin E2 PMID: 25989136
24. Data show that mesenchymal stem cells (MSCs) administration alleviated airway inflammation and emphysema through the down-regulation of cyclooxygenase-2 (COX-2) via p38 and ERK MAPK pathways. PMID: 25736434
25. increased COX-2-dependent vasoconstriction contributes to renal endothelial dysfunction through enhanced reactive oxygen species generation in obesity. PMID: 25841778
26. The aim of this study was to determine the role of COX-2 in the regulation of blood pressure and to define the mechanisms in two kidney one-clip hypertensive (2K1C) rats PMID: 25846103
27. Treatment with probiotics has the potential of providing protection against colon cancer by down-regulating the COX-2 expression as one of the protective mechanisms. PMID: 25811420
28. TNF-alpha-induced COX-2 and PGE2 stimulate Wnt signaling and activate Wnt target genes PMID: 26123748
29. Increased COX2 expression after l-DOPA long-term treatment in Parkinsonian-like rats could contribute to the development of dyskinesia. PMID: 26009769
30. Concomitant use of alpha-lipoic acid and cyclosporine significantly increased nitric oxide production, cyclooxygenase-2 and miR-210 gene expression in rat colon. PMID: 26276312
31. E2-BSA induced the COX-2 expression and consequent PGE2 and PGF2alpha release in rat OECs. These effects are mediated through GPR30-derived EGFR transactivation and PI-3K/Akt cascade leading to NF-kappaB activation PMID: 26241029
32. Low-level laser therapy decreases Achilles tendon inflammatory process mediated by Il1b and COX-2. PMID: 25070591
33. COX-2 oxidative metabolism is a key regulator of the anandamide-mediated decidual remodeling in pregnancy. PMID: 26335727
34. Our results demonstrated that ventricular hypertrophy abrogated isoflurane-induced delayed cardioprotection by alteration of iNOS/COX-2 pathway PMID: 25400168
35. Hypomethylation of PTGS2, and hypermethylation of APC2 may be causally linked to the etiology of oral cancer in a rat model. PMID: 25635769
36. Clathrin-dependent internalization of the angiotensin II ATA receptor links receptor internalization to COX-2 protein expression in rat aortic vascular smooth muscle cells PMID: 25542758
37. Report design of benzimidazole analogs endowed with oxadiazole as selective COX-2 inhibitors. PMID: 25303727
38. Cadmum induced release of reactive oxygen species derived from NADPH oxidase may be due to the increased local release of angiotensin II and the release of vasoconstrictor prostanoids derived from the COX-2 pathway. PMID: 23973752
39. Data suggest that cyclooxygenase-2 (COX2) and NADPHox are potential therapeutic targets to decrease testosterone-driven cardiovascular risk. PMID: 25700020
40. data propose that an increase in COX-2 expression in ventral CA1 following trauma is likely due to its attenuated degradation. PMID: 25058273
41. Data (including data from studies in transgenic rats) suggest that attenuation of circadian clock system, especially its core component Rev-erb-alpha, contributes to induction of Ptgs2 in endometrial stromal cells during decidualization/placentation. PMID: 25648833
42. Nitric oxide synthase (NOS) and cyclooxygenase (COX) isoform expression patterns were determined in femoral artery of obese Zucker rats. PMID: 25216050
43. Reflux of duodenal contents induces COX2 expression and increases prostaglandin synthesis in dysplastic and cancer tissues PMID: 24914375
44. ischemia reperfusion injury significantly increased the COX2 expression, PGI2 and TXA2 levels, and the PGI2/TXA2 ratio in rat hippocampus in a time-dependent manner PMID: 25388440
45. The present study showed that the group receiving Vitamin E supplementation at 3x recommended daily intake displayed reduced COX2 expression. PMID: 25123248
46. during the early phase of ANG II-dependent hypertension, the increased (P)RR and COX-2 expression in the renal medulla may contribute to attenuate the vasoconstrictor effects of ANG II on renal hemodynamics PMID: 25143455
47. The data suggest that local hypertonicity in the medullary thick ascending limb is associated with an increase in COX-2 expression concomitant with elevated EP3 receptor expression, which limits COX-2 activity in this segment of the nephron. PMID: 25080527
48. Elevated COX-2 expression during hypoxia where angiogenesis occurs and re-oxygenation, when micro-vessels regress, identifies this protein as a vascular remodeling molecule crucial for angioplasticity. PMID: 24796880
49. Fibroblasts activated by hepatoma cell supernatant express COX-2 and HGF at higher levels. PMID: 24815169
50. Suggest lead-associated inflammatory neurotoxicity occurs via activation of pro-inflammatory NFAT3/COX-2 axis. PMID: 25193092

顯示更多

收起更多

Microsome membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein. Nucleus inner membrane; Peripheral membrane protein. Nucleus outer membrane; Peripheral membrane protein.

Prostaglandin G/H synthase family

Expressed throughout the forebrain in discrete populations of neurons and is enriched in the cortex and hippocampus.

KEGG: rno:29527

STRING: 10116.ENSRNOP00000003567

UniGene: Rn.217585