Disease relevance of COX1

• CONCLUSIONS: Chronic ischemia increased bladder 5-lipoxygenase, and COX-1 and COX-2 protein expression, and altered leukotriene and PG production [1].
• COX-2, but not COX-1, protein levels markedly increased following hypoxia [2].
• OBJECTIVE: To evaluate the effects of COX-1 and/or COX-2 inhibition in a model of chronic esophagitis in rabbits [3].
• In balloon-injured, atherosclerosis-free porcine arteries, COX-1 gene transduction increases PGI2 production, induces durable vasodilation, and reduces thrombus formation [4].

High impact information on COX1

• Neither NS-398 nor celecoxib lowered PGE(2) or 6-keto-PGF(1alpha) levels in the nonischemic region of preconditioned rabbits, indicating that constitutive COX-1 activity was unaffected [5].
• Conversely DRE activity was only inhibited by the COX2-selective inhibitor SC236 but not by a COX1-selective NSAID (SC560) [6].
• COX-1 and -2 protein expression in corneal epithelium was determined by Western blot [7].
• COX-1 was detected as the major isoform by immunoblot analysis in extracts from aortas of normal and 8 week cholesterol-fed animals with COX-2 being induced in atherosclerotic plaques from cholesterol-fed animals [8].
• RESULTS: Early inflammatory arthritis led to an overall upregulation of most genes assessed, but a downregulation of some genes (iNOS, HAS-2, COX-1) in some tissues [9].

Biological context of COX1

• In contrast to diclofenac (IC50 = 0.12 microM), nepafenac exhibited only weak COX-1 inhibitory activity (IC50 = 64.3 microM) [10].
• CONCLUSIONS: The effectiveness of COX-1 in preventing restenosis and preserving normal blood flow 28 days after injury results from increased lumen area caused by durable vasodilation [4].

Anatomical context of COX1

• In cultured vascular smooth muscle cells, ATV reduced the expression of COX-2 mRNA induced by IL-1beta and TNF-alpha without affecting COX-1 expression [11].
• With the use of immunohistochemical analysis, both COX-1 and COX-2 were detected in endothelium and smooth muscle of small mesenteric arteries [12].
• Furthermore, progesterone and 17beta-estradiol suppressed the IL-1alpha-augmented COX-2 production but not the constitutive production of COX-1 in rabbit uterine cervical fibroblasts [13].
• RESULTS: Prostaglandins are derived from COX-1 activity in the normal esophagus [3].
• CONCLUSIONS: COX-1 activity is constitutive in the rabbit esophageal mucosa, but both COX-2 and COX-1 activity are increased under the impact of acidified pepsin [3].

Associations of COX1 with chemical compounds

• We investigated the effects of licofelone on cardiovascular derangements and production of thromboxane (Tx)A(2) induced by the inflammatory agonist n-formyl-methionyl-leucyl-phenylalanine (fMLP) in the rabbit, in comparison with those of aspirin or rofecoxib, inhibitors of COX-1 and COX-2, respectively [14].
• SC-58236, a COX2-selective inhibitor, but not SC-58560, a COX1 inhibitor, preferentially blocks PGE2 synthesis in MICs [15].
• Celecoxib (Celebrex), valdecoxib (Bextra), and rofecoxib (Vioxx) are nonsteroidal antiinflammatory drugs (NSAIDs) due to selective inhibition of inducible cyclooxygenase COX-2 while sparing inhibition of constitutive COX-1 [16].
• The cyclooxygenase (COX) inhibitors indomethacin (10 microM), NS-398 (10 microM, selective for COX-2), and SC-560 (100 nM, selective for COX-1) caused a marked rightward shift of concentration responses to AA [12].
• Isoflurane did not alter COX-1 and COX-2 protein expression [17].

Analytical, diagnostic and therapeutic context of COX1

• 3. RT PCR was done on total RNA for mRNA expression of the constitutive (COX-1) and inducible cyclooxygenase (COX-2) [18].
• The mRNA levels for COX-1 and COX-2 in the iris-ciliary body were determined by real-time polymerase chain reaction [19].

References