Disease relevance of Ptgs1

• Prostaglandins (PGs) generated by the enzyme cyclooxygenase (COX) have been implicated in the pathological renal hemodynamics and structural alterations in diabetes mellitus, but the role of individual COX isoenzymes in diabetic nephropathy remains unknown [1].
• BACKGROUND & AIMS: The critical role of cyclooxygenase (COX) products in maintenance of renal function in cirrhosis with ascites discourages the use of nonsteroidal anti-inflammatory drugs in this disease [2].
• This study evaluated the relationship between inflammatory mediators, COX expression, and pathological changes in experimental alcoholic liver disease [3].
• Epidemiological and laboratory studies suggest that nonsteroidal antiinflammatory drugs reduce the risk of colon cancer and that the inhibition of colon carcinogenesis is mediated through modulation of prostaglandin production by cyclooxygenase (COX) isozymes (COX-1 and -2) [4].
• In addition, a nonselective (acetylsalicylic acid) or selective cyclooxygenase (COX) 1 inhibitor (SC-560) completely abrogated the 8-iso-PGF(2alpha) and PGF(2alpha) formation in kidneys subjected to ischemia [5].

Psychiatry related information on Ptgs1

• The effects of different COX and NOS inhibitors on the intestinal motor activity were tested. mRNA expression of COX-1 was not modified by inflammation, whereas mRNA expression of neuronal NOS was reduced in all indomethacin-treated rats [6].
• In the current study, we sought to determine the role of COX isoenzymes after laparotomy, examining spontaneous exploratory behavior rather than withdrawal reflexes [7].
• In this study, we investigated the therapeutic potential for Alzheimer's disease of mefenamic acid, a commonly used NSAID that is a cyclooxygenase-1 and 2 inhibitor with only moderate anti-inflammatory properties [8].
• Extending the current view on the treatment of drug dependence, these results indicate that endocannabinoid-activating substances as well as cyclooxygenase inhibitors may be promising as antirelapse agents [9].
• The above results indicate that in rats subjected to a prolonged period of dietary restriction, the uterine glycogen becomes responsive to the effects of cyclooxygenase and lipoxygenase inhibitors, suggesting the operation of some regulatory mechanism during critical periods of nutrition [10].

High impact information on Ptgs1

• 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].
• Furthermore, opioid inhibition of GABAergic synaptic transmission is potentiated by inhibitors of the enzymes cyclooxygenase and 5-lipoxygenase, presumably because more arachidonic acid is available for conversion to 12-lipoxygenase products [12].
• Blockade of the cyclooxygenase pathway did not inhibit arachidonic acid-induced channel activation [13].
• The ulcerogenic actions of PAF are not attributable solely to its hypotensive actions and were not mediated via effects on platelets or cyclooxygenase products, nor via histamine H1, H2 or alpha-adrenergic receptors [14].
• Anti-inflammatory glucocorticoids inhibit prostaglandin (PG) biosynthesis by preventing arachidonic acid release from phospholipids rather than inhibiting the cyclooxygenase [15].

Chemical compound and disease context of Ptgs1

• 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].
• Additional rats received Pio (10 mg.kg-1.day-1) for 3 days and intravenous SC-58125 [a cyclooxygenase-2 (COX-2) inhibitor] or SC-560 (a COX-1 inhibitor) 15 min before ischemia [17].
• To elucidate the role of cyclooxygenase (COX)-2 in ulcer healing, we compared the effects of NS-398 (COX-2-selective inhibitor) and indomethacin (nonselective COX inhibitor) on the healing of acetic acid-induced gastric ulcers in rats [18].
• This study examines the role played by cyclooxygenase (COX) isoforms (COX-1 and -2) in the regulation of colonic neuromuscular function in normal rats and after induction of colitis by 2,4-dinitrobenzenesulfonic acid (DNBS) [19].
• We hypothesized that COX inhibitors may attenuate endothelial dysfunction during sepsis, as measured by receptor-mediated bradykinin (BK)-induced vasoconstriction and/or receptor-independent hypoxic pulmonary vasoconstriction (HPV) [20].

Biological context of Ptgs1

• BACKGROUND & AIMS: Inflammatory stimuli and lipid peroxidation up-regulate cyclooxygenase (COX)-2 [3].
• Down-regulation of COX-1 may result in decreased synthesis of cytoprotective eicosanoids and additionally exacerbate liver injury [3].
• 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].
• Here, we examined the effects of two oxidative stresses, hydrogen peroxide (H2O2) and the anthracycline doxorubicin on the activity of ERK1/2 and the expression of COX isoforms and PG formation in neonatal rat primary cardiomyocytes [21].
• This is the first example of neurotrophic factor regulation of cyclooxygenase and may have important implications for determination of the differentiated phenotype in PC12 cells [22].

Anatomical context of Ptgs1

• COX-1 mRNA was decreased in Kupffer cells in rats with the most severe liver injury [3].
• Animals were sacrificed 1, 12, or 36 weeks after the last AOM or saline injection, and their colonic mucosa, as well as the grossly visible colon tumors from rats sacrificed 36 weeks after the last AOM injection, were analyzed for the expression levels of COX-1 and COX-2 [23].
• 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 [24].
• In this investigation, we examined the expression of cox1 and cox2 mRNA in rat aorta following balloon deendothelialization (BDE) in vivo and in rat aortic smooth muscle cells (SMC) after serum stimulation in vitro [25].
• Ag stimulation of cultured RBL-2H3 mast cells resulted in increased expression of cyclooxygenase (COX-2) protein and message [26].

Associations of Ptgs1 with chemical compounds

• These eicosanoids, formed by cyclooxygenase-dependent metabolism of arachidonic acid, are important physiologic mediators of renal glomerular hemodynamics and tubular sodium and water reabsorption [27].
• 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 [3].
• To provide an understanding of the mechanism(s) of dietary fat-induced modulation of colon tumor development, we have analyzed the expression of cyclooxygenase (COX), an enzyme that catalyzes the metabolism of omega-3 and omega-6 polyunsaturated fatty acids in a critical step in prostaglandin biosynthesis [23].
• Serum-treated SMC also generated greater amounts of cyclooxygenase-dependent metabolites than quiescent SMC as evidenced by marked increases in prostaglandin E2 content in conditioned media [25].
• Both the Cox-1 mRNA, quantified in the whole lung homogenate, and the cellular localization of Cox-1 were unchanged in response to LPS [28].

Physical interactions of Ptgs1

• The results indicate that ADM interacts with COX to yield prostanoids, which mediate its negative inotropic effect in LPS-treated rat ventricular myocytes [29].

Regulatory relationships of Ptgs1

• The inhibition of COX-1 up-regulates COX-2 expression, and this may be a key to NSAID-induced intestinal damage [30].
• Immunoblot analysis using isoform-specific antibodies showed that the inducible cyclooxygenase enzyme (COX-2) was expressed by 4 h in LPS and IL-1beta treated cells while the constitutive COX-1 remained unaltered in its expression [31].
• The role of endothelin-1 to regulate prostaglandin endoperoxide synthase (PGHS)-1 and -2 gene expression and protein synthesis was evaluated in cultured mesangial cells [32].
• Interleukin 1 alpha (IL-1 alpha) stimulates prostaglandin production and cyclooxygenase activity in endometrial stromal cells isolated from the uteri of ovariectomized rats that have been sensitized for the decidual cell reaction [33].
• We hypothesized that cyclooxygenase (COX) products influence the formation of MCP-1 and affect inflammatory cell recruitment in glomerulonephritis [34].

Other interactions of Ptgs1

• Rats selected at either active or reactive phases and from 2 to 60 days after indomethacin treatment were used. mRNA expression of both constitutive and inducible NOS and COX isoforms in each phase was evaluated by RT-PCR and cellular enzyme localization by immunohistochemistry [6].
• These results suggest that COX-1 and cNOS play as the respective key enzyme responsible for producing PG and NO following the duodenal acidification, both of which are involved in the mechanism for the acid-induced HCO3- secretion in the duodenum [35].
• The mRNA levels of cPLA2, COX-2 and mPGES-1 in the bladder papilloma and TCC were significantly higher than those in normal bladder (P<0.01), while the mRNA levels of COX-1 and mPGES-2 in TCC were unchanged compared with normal bladder [36].
• Laparotomy stimulated HO activity, whereas gut manipulation led to an excessive constitutive NOS stimulation accompanied by augmented prostanoid synthesis by COX-1 [37].
• Lipopolysaccharide-induced increase of prostaglandin E(2) is mediated by inducible nitric oxide synthase activation of the constitutive cyclooxygenase and induction of membrane-associated prostaglandin E synthase [38].

Analytical, diagnostic and therapeutic context of Ptgs1

• Based on RT-PCR and Northern blot analysis, resting zone chondrocytes express mRNAs for both Cox-1 and Cox-2 [39].
• Although AT did not affect COX-1 mRNA levels 1 hour after reperfusion, it inhibited the I/R-induced increases in hepatic tissue levels of both PGE(2) and COX-2 mRNA 6 hours after reperfusion [40].
• Rats were perfused at 1, 2, 3, 5, and 7 days after incision, and COX-1 immunohistochemistry was performed on L3 to S2 spinal cord and gracile nucleus sections [41].
• Using competitive polymerase chain reaction, we determined whether COX gene expression was altered in colorectal tumours and in regions of adjacent and distant macroscopically normal intestine, from vehicle or NSAID treated rats [42].
• Mucosal PGE2 levels were determined by enzyme immunoassay, whereas the gene expression of COX isozymes was examined by reverse transcription-polymerase chain reaction [30].

References