Disease relevance of COX1

• Inhalation of NO during endotoxemia increased the constitutive COX (COX-1) expression, and the circulating TxB(2) and PGF(2alpha) increased further after INO withdrawal [1].
• As hypoxia is reported to stimulate the expression of COX-2, we have investigated the effects of bypass circulation and cardioplegic arrest on the expression COX-1 and COX-2 in the myocardium of porcine hearts [2].

High impact information on COX1

• Injured tissues treated with the selective COX-1 inhibitor SC-560 (5x10(-6) M) or the COX-2 inhibitor NS-398 (5x10(-6) M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF1alpha compared with untreated tissues [3].
• CONCLUSIONS: The results suggest that recovery of resistance is triggered by PGE and PGI2, which may be elaborated by either COX-1 or COX-2 [3].
• Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COX-1 and COX-2 [3].
• Thromboxane B2 (TXB2, the stable metabolite of TXA2) was measured as a likely indicator of COX-1 activity [3].
• In support of this concept, COX-1, but not COX-2, inhibition was effective in restoring normal mucosal prostaglandin levels [4].

Biological context of COX1

• However, no upregulation of COX-1 protein was detected [5].
• COX-2 rather than COX-1 seems to be the primary enzyme responsible for modulated PGs production at the time of luteolysis in cyclic and during implantation in pregnant animals [5].
• In contrast to COX-1, a positive immunostaining reaction for COX-2 was detected only on days 12-16 after ovulation and on days 14-16 of pregnancy [5].
• CONCLUSIONS: Data suggest that increased COX-1- and COX-2-catalyzed prostaglandin synthesis contribute equivalently to the downregulation of retinovascular EP1, EP3, and FP receptors and their vasoconstrictor functions in newborn pigs; the EP2 receptor was not significantly influenced by ontogenic alterations in prostaglandin levels [6].
• These results suggest that H2O2 induces endothelium-dependent vasodilation through COX-1-mediated release of PGE2 and also directly relaxes smooth muscle by hyperpolarization through KCa channel activation [7].

Anatomical context of COX1

• Immunohistochemistry showed that COX-1 and COX-2 are constitutively present in normal guinea pig trachea, particularly in the epithelial layer, and that COX-2 expression is enhanced in OVA-sensitized animals both in epithelial and subepithelial tissues [8].
• In conclusion, these results indicate specific patterns of COX-1 and COX-2 expression in the porcine endometrium throughout the oestrous cycle and early pregnancy [5].
• COX-1 and COX-2 were localized in the luminal and glandular epithelium as well as in the uterine stroma [5].
• Retinal vessel EP1, EP3, and FP receptor densities increased approximately threefold after treatments with COX-1 or COX-2 inhibitors, and five- to sixfold after ibuprofen treatment [6].
• Abundances of both COX-1 and prostacyclin synthase were reduced, whereas abundances of both COX-2 and thromboxane synthase were unaltered in pulmonary arteries from hypoxic piglets [9].

Associations of COX1 with chemical compounds

• NOS inhibition by l-N(G)-nitro-arginine methyl ester (l-NAME) did not affect histamine-induced contraction but reversed the increase caused by COX-1 blockade while not modifying the enhancement associated with COX-2 inhibition [8].
• At slaughter, endometrial tissue was collected to determine endometrial expression levels of GM-CSF mRNA, cyclooxygenase-1 (COX1) and -2 (COX2) and to evaluate in vitro endometrial secretion of prostaglandin E2 (PGE2) secretion [10].
• METHODS: Newborn pigs were treated intravenously every 8 hours for 48 hours with saline, 40 mg/kg nonselective COX inhibitor ibuprofen, 80 mg/kg COX-1 inhibitor valeryl salicylate, or 5 mg/kg DuP697 and 5 mg/kg NS398, COX-2 inhibitors [6].
• Inhibition of the COX-1, but not the COX-2 pathway, attenuated H2O2-induced dilation similarly to indomethacin [7].
• Moreover, IDM decreased the frequency of exocytotic events stimulated by ionomycin, suggesting that COX-1 activity is stimulated by an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) [11].

Other interactions of COX1

• The cultures underwent Western Blot analysis for smooth muscle cell content of COX-1, COX-2, Prostacyclin Synthase (PS), or were incubated with CCK at 10(-8)M or 10(-6)M with and without indomethacin for 1h and analyzed for release of 6-keto-PGF1alpha, PGE2 and TxB2 by EIA [12].

Analytical, diagnostic and therapeutic context of COX1

• Immunofluorescence for COX-1 in endothelium was minimal in cerebral arteries and arterioles from control animals and did not show an increase in animals exposed to anoxic stress [13].
• Cerebral vessels were fixed in 4% formalin and paraffin embedded, and constitutive and inducible COX (COX-1 and COX-2, respectively) levels were assessed using indirect immunofluorescence [13].
• Both COX-1 and COX-2 proteins were detected by Western blot analysis in the myocardial specimens of control hearts [2].
• In survivors, Mphi COX-1 peaked at > 100 times baseline in both right BAL and left BAL by 60 minutes (before resuscitation) [14].
• Expression of eNOS, iNOS, and inducible (COX-2) and constitutive (COX-1) cyclooxygenase was examined with Western blotting and reverse transcription polymerase chain reaction [15].

References