Psychiatry related information on COX1

• The assay can be used to assess the relative selectivity of plant-derived inhibitors on COX-1 and COX-2 Assay conditions were optimized for both enzymes with respect to concentration of cofactors (l-epinephrine, reduced glutathione, and hematin), activation time (enzyme and cofactors), reaction time, and pH [1].

High impact information on COX1

• These findings indicate that physiologic levels of estrogen cause upregulation of COX-1 expression and PGI2 synthesis in fetal PAEC via activation of PAEC ER [2].
• We therefore studied the direct effects of estrogen on COX-1 expression in ovine fetal pulmonary artery endothelial cells (PAEC) [2].
• The hormone estrogen may play a role in COX-1 upregulation since fetal estrogen levels rise dramatically during late gestation and estrogen enhances PGI2 synthesis in nonpulmonary vascular cells [2].
• The estrogen receptor (ER) antagonist ICI 182,780 fully reversed the effects of the hormone on COX-1 protein expression and on arachidonic acid-stimulated PGI2 synthesis, and ER expression was evident in the PAEC by immunoblot analysis [2].
• Prostacyclin (PGI2) is a key mediator of pulmonary vasodilation in the perinatal period and its synthesis in the pulmonary vasculature increases markedly during late gestation due to enhanced expression of the rate-limiting enzyme cyclooxygenase-1 (COX-1) [2].

Biological context of COX1

• We have analyzed sequence and structural diversity of sheep COX-1 and mouse COX-2 proteins by Active Site Profiling (ASP) [3].
• Here we have examined the relative importance of cyclo-oxygenase-1 (COX1) and cyclo-oxygenase-2 (COX2) for PGE(2) formation in the foetal lamb ductus (0.65 gestation onwards) [4].
• COX-1 mRNA stability was unchanged, suggesting that the upregulation is mediated at the level of transcription [2].
• Thus, the developmental upregulation of PGI2 synthesis is conserved in early-passage PAEC and pulmonary VSM, and is related to a maturational increase in COX-1 gene expression [5].
• Immunohistochemical localization of COX-1 was endothelium > VSM, with both cell types showing an increase in COX-1 during the third trimester of pregnancy [6].

Anatomical context of COX1

• 2. Using fluorescence microscopy and immunogold staining, COX1 appeared more abundant than COX2 in endothelial and smooth muscle cells, and this difference was greater before-term [4].
• Inside muscle cells, COX1 and COX2 immunoreactivity was located primarily in the perinuclear region [4].
• We conclude that the pregnancy-induced increases in prostacyclin production by uterine arteries is largely due to a dramatic increase in expression of COX-1 mRNA and associated protein predominantly occurring in the uterine artery endothelium and, to a lesser extent, in the VSM [6].
• Further studies with the cultured cell model will enable determination of the factors that directly regulate COX-1 expression in the developing pulmonary vasculature [5].
• Endothelial and vascular smooth muscle (VSM) COX-1 protein levels and uterine artery endothelial cell COX-1 mRNA levels were compared [7].

Associations of COX1 with chemical compounds

• The present study was performed to test the relative roles of prostaglandin endoperoxide synthases-1 and -2 (PGHS-1 and 2, or COX-1 and 2) as potential mediators of this interaction [8].
• METHODS: Chronically catheterized and instrumented fetal sheep were subjected to transient brachiocephalic occlusion (BCO) after intracerebroventricular injection of resveratrol (PGHS-1 or COX-1 inhibitor), nimesulide (PGHS-2 or COX-2 inhibitor), or vehicle [8].
• 3. The COX2 inhibitor L-745,337 (1--10 microM) contracted the isolated ductus at term, the response being almost as high as that to indomethacin (dual COX1/COX2 inhibitor) over the same dose-range [4].
• Exposure to estradiol-17beta (E2beta, 10(-)10 to 10(-)6 M) caused a dose-related increase in COX-1 mRNA expression that was evident after 48 h and maximal at 10(-)8 M (fourfold increase) [2].
• Endothelial vasodilator production by uterine and systemic arteries. VIII. Estrogen and progesterone effects on cPLA2, COX-1, and PGIS protein expression [9].

Regulatory relationships of COX1

• NOC7 activated the COX-1 activity but inhibited the COX-2 activity at concentrations ranging from 1 to 50 microM [10].

Other interactions of COX1

• Aspirin revealed a similar COX-1 deleterious action, since only when both COX-1 and COX-2 were inhibited, LP was put in evidence adding functional improvement over that obtained in NP hearts treated with aspirin [11].

Analytical, diagnostic and therapeutic context of COX1

• RT-PCR failed to detect any change in levels of nNOS, eNOS, iNOS, COX-1 or COX-2 mRNAs [12].
• Using immunohistochemistry and Western analysis, the primary location of COX-1 protein was the endothelium; that is, we observed 2.2-fold higher COX-1 protein levels in intact versus endothelium-denuded uterine artery and a 6.1-fold higher expression in the endothelium versus VSM (P < 0.05) [7].
• Arteries were procured on Day 10, and cPLA2, COX-1, and PGIS protein were measured by Western immunoblot analysis in endothelial isolated proteins and vascular smooth muscle (VSM) [9].

References