Disease relevance of Ptgs2

• Therapeutic administration of a selective COX-2 inhibitor, SC-58125, rapidly reversed paw edema and reduced the level of PGE2 in paw tissue to baseline [1].
• The recent development of selective COX-2 inhibitors opens new avenues for the use of these compounds in decompensated cirrhosis [2].
• In this study, we investigated the effects of bile acids and duodenal reflux on COX-2 expression in cultured esophageal cells and tissue, respectively [3].
• Selective inhibition of cyclooxygenase 2 spares renal function and prostaglandin synthesis in cirrhotic rats with ascites [2].
• Enhanced cyclooxygenase-2 gene expression in alcoholic liver disease in the rat [4].

Psychiatry related information on Ptgs2

• It has been reported that the expression of cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptor-gamma (PPARgamma) is elevated in Alzheimer's disease, and certain nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce the risk and delay the onset of Alzheimer's disease [5].
• Exploratory locomotor activity was measured on the first postoperative day after intrathecal injection of dimethyl sulfoxide (vehicle) or COX-1 (SC-560) or COX-2 (NS-398) inhibitors [6].
• If targeting this part of the 'AA cascade' accounts for their therapeutic action, non-steroidal anti-inflammatory drugs or selective COX-2 inhibitors might prove effective in bipolar disorder [7].
• Enhancement of slow-wave sleep by tumor necrosis factor-alpha is mediated by cyclooxygenase-2 in rats [8].
• The developmental profile of COX-2 expression in dendrites follows well known histogenetic gradients and coincides with the critical period for activity-dependent synaptic remodeling [9].

High impact information on Ptgs2

• Prostaglandin endoperoxide synthase 2, also referred to as cyclooxygenase 2 (COX-2), is a key enzyme in the conversion of arachidonic acid to prostaglandins and other eicosanoids [10].
• Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2 [10].
• The selective COX 2 inhibitor NS-398 and the dual COX 1/COX 2 inhibitor indomethacin inhibited inflammation at 2 hours but significantly exacerbated inflammation at 48 hours [11].
• In this model, COX 2 protein expression peaked initially at 2 hours, associated with maximal prostaglandin E2 synthesis [11].
• Inhibition of cyclooxygenase-2 potentiates retrograde endocannabinoid effects in hippocampus [12].

Chemical compound and disease context of Ptgs2

• We conclude that LPS-induced Cox-2 regulation occurs in a complex, cell-specific manner, which may be relevant for pathogenetic sequelae in septic lung injury and acute respiratory failure [13].
• We examined the effect of an angiotensin II receptor inhibitor (AT(1)) losartan, independent from its effects on blood pressure, on nitric oxide synthase (NOS) isoforms and cyclooxygenase-2 (COX-2) expression and the significance of this interaction on interstitial fibrosis in UUO [14].
• Effect of flosulide, a selective cyclooxygenase 2 inhibitor, on passive heymann nephritis in the rat [15].
• Inhibition of prostaglandin synthesis by traditional NSAIDs such as indomethacin and diclofenac which non-selectively inhibit both PGHS-1 and PGHS-2, causes gastric and intestinal ulceration and delays gastric ulcer healing in chronic models [16].
• In this study we evaluated cyclooxygenase-2 protein immunocytochemically and found markedly enhanced immunostaining primarily in olfactory-limbic regions at 2, 6 and 24 h following kainate-induced status epilepticus [17].

Biological context of Ptgs2

• PG production was associated with upregulation of COX-2 mRNA and protein in the affected paws [1].
• The intrarenal distribution of COX-2 and its increased expression in response to sodium restriction suggest that in addition to its proposed role in inflammatory and growth responses, this enzyme may play an important role in the regulation of salt, volume, and blood pressure homeostasis [18].
• Immunoblotting and immunohistochemistry were performed to evaluate the effects of duodenal reflux on COX-2 expression and cell proliferation in esophageal tissue [3].
• Pathological analyses and measurements of lipid peroxidation, tumor necrosis factor (TNF)-alpha, COX-1 and COX-2 messenger RNA (mRNA), endotoxin, and liver and plasma thromboxane were performed [4].
• RESULTS: Administration of SC-236 to cirrhotic animals did not produce significant renal effects, whereas administration of the nonselective COX-1/COX-2 inhibitor, ketorolac, resulted in a marked reduction in urine volume, urinary excretion of prostaglandins, and glomerular filtration rate and in a significant impairment in renal water metabolism [2].

Anatomical context of Ptgs2

• In situ hybridization and immunohistochemistry indicated that renal cortical COX-2 expression was localized to the macula densa of the juxtaglomerular apparatus and to adjacent epithelial cells of the cortical thick ascending limb of Henle [18].
• Immunoblots of microsomes isolated from kidney cortex and papilla indicated immunoreactive COX-2 in both locations [18].
• Furthermore, inhibition of COX-2 resulted in a reduction of the inflammatory cell infiltrate and decreased inflammation of the synovium [1].
• Duodenal reflux induces cyclooxygenase-2 in the esophageal mucosa of rats: evidence for involvement of bile acids [3].
• METHODS: Immunoblotting and Northern blotting were used to assess the effects of bile acids on COX-2 expression in esophageal cell lines [3].

Associations of Ptgs2 with chemical compounds

• Immunoreactive COX-2 was increased in D rats compared with C rats and normalized by improved glycemic control [19].
• Indomethacin, but not a highly selective COX-2 inhibitor or an inducible NOS inhibitor, abolished long-term endotoxin-induced gastric resistance to injury [20].
• RESULTS: Unconjugated bile acids were about fivefold more potent inducers of COX-2 messenger RNA, COX-2 protein, and prostaglandin synthesis than conjugated bile acids [3].
• The results of this study provide evidence, for the first time, that a specific COX-2 inhibitor, celecoxib, possesses strong chemopreventive activity against colon carcinogenesis [21].
• HFCO further enhanced the AOM-induced COX-2 expression [22].

Physical interactions of Ptgs2

• Treatment with a p38 MAPK inhibitor, PD169316, or transfection with a dominant-negative p38 MAPK construct reversed the effect of CD or ceramide to stabilize COX-2 mRNA [23].
• The distribution of cyclooxygenase-2 and membrane bound prostaglandin E synthase messenger RNA expressing cells suggests major involvement of non-neuronal cells in spinal prostaglandin biosynthesis [24].
• The results suggest that the anti-inflammatory properties of oxyresveratrol might be correlated with inhibition of the iNOS expression through down-regulation of NF-kappaB binding activity and significant inhibition of COX-2 activity [25].
• A docking experiment to determine the orientation of (Z)-9c within the COX-2 binding site showed that the linear p-N3 group inserts into the COX-2 2 degrees-pocket, where it undergoes an ion-ion (electrostatic) interaction with Arg513 [26].

Regulatory relationships of Ptgs2

• We conclude that in MC, ET-1 induces PGHS-2 through a protein tyrosine kinase-dependent pathway [27].
• Gastrin stimulates cyclooxygenase-2 expression in intestinal epithelial cells through multiple signaling pathways. Evidence for involvement of ERK5 kinase and transactivation of the epidermal growth factor receptor [28].
• Interleukin-13 enhances cyclooxygenase-2 expression in activated rat brain microglia: implications for death of activated microglia [29].
• When COX-2 was induced in response to activation of EGFR, the activated astrocytes produced and released the proinflammatory mediator, PGE(2), in a time-dependent manner [30].
• The inhibition of COX-1 up-regulates COX-2 expression, and this may be a key to NSAID-induced intestinal damage [31].
• Forced expression of CUGBP2 or constitutively active c-Src leads to stabilization of co-expressed COX-2 mRNA [32].

Other interactions of Ptgs2

• In conclusion, we documented an increase in renal cortical COX-2 protein expression associated with a different renal hemodynamic response to selective systemic COX-2 inhibition in D as compared with C animals, indicating a role of COX-2-derived PG in pathological renal hemodynamic changes in diabetes [19].
• Elevated levels of cyclooxygenase-2 in antigen-stimulated mast cells is associated with minimal activation of p38 mitogen-activated protein kinase [33].
• Cytosolic phospholipase A2 is required for cytokine-induced expression of type IIA secretory phospholipase A2 that mediates optimal cyclooxygenase-2-dependent delayed prostaglandin E2 generation in rat 3Y1 fibroblasts [34].
• Studies using an anti-type IIA sPLA2 antibody, sPLA2 inhibitors, and a type IIA sPLA2-specific antisense oligonucleotide revealed that IL-1 beta/TNF alpha-induced delayed PGE2 generation by these cells was largely dependent on inducible type IIA sPLA2, which was functionally linked to inducible COX-2 [34].
• ET-1 induction of PGHS-2 protein was accompanied by a sustained enhancement of enzymatic activity assessed by conversion of arachidonic acid to prostaglandin E2 [27].

Analytical, diagnostic and therapeutic context of Ptgs2

• Selective inhibition of cyclooxygenase (COX)-2 reverses inflammation and expression of COX-2 and interleukin 6 in rat adjuvant arthritis [1].
• Inhibition of NO production in LPS-treated macrophages by either the L-arginine analogue N(G)-monomethyl-L-arginine (L-NMMA) or aminoguanidine was accompanied by an additional enhancement of Cox activity parallel to the expression of Cox-2 protein analyzed by Western blot [35].
• Therefore, inhibition of COX-2-mediated lipid hydroperoxide formation offers a potential therapeutic alternative to COX-2 inhibitors in chemoprevention strategies [36].
• Specific immunoprecipitation of Cox-2 showed a pattern of protein expression similar to that observed in intact cells [35].
• To understand the molecular mechanism of Cox-2 action we used adenovirus-mediated transfer of rat Cox-2 cDNA into renal rat mesangial cells and determined the differential gene expression using cDNA microarrays [37].

References