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Gene Review

COX1  -  cytochrome c oxidase subunit I

Oryctolagus cuniculus

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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


Associations of COX1 with chemical compounds


Analytical, diagnostic and therapeutic context of COX1


  1. Increased leukotriene and prostaglandin release, and overactivity in the chronically ischemic bladder. Azadzoi, K.M., Shinde, V.M., Tarcan, T., Kozlowski, R., Siroky, M.B. J. Urol. (2003) [Pubmed]
  2. COX-2 lack of function in hypoxia-induced ocular surface inflammation. Schwartzman, M.L., Bonazzi, A., Mieyal, P., Mezentsev, A., Abraham, N.G., Dunn, M.W. Thromb. Res. (2003) [Pubmed]
  3. Selective COX-2 inhibition is associated with decreased mucosal damage induced by acid and pepsin in rabbit esophagitis. Lanas, A., Jiménez, P., Ferrández, A., Escartín, A., Arenas, J., Esteva, F., Ortego, J. Inflammation (2003) [Pubmed]
  4. Local gene transduction of cyclooxygenase-1 increases blood flow in injured atherosclerotic rabbit arteries. Liu, Q., Chen, Z.Q., Bobustuc, G.C., McNatt, J.M., Segall, H., Pan, S., Willerson, J.T., Zoldhelyi, P. Circulation (2005) [Pubmed]
  5. Cyclooxygenase-2 mediates the cardioprotective effects of the late phase of ischemic preconditioning in conscious rabbits. Shinmura, K., Tang, X.L., Wang, Y., Xuan, Y.T., Liu, S.Q., Takano, H., Bhatnagar, A., Bolli, R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  6. Peroxisome proliferator-activated receptor delta activation promotes cell survival following hypertonic stress. Hao, C.M., Redha, R., Morrow, J., Breyer, M.D. J. Biol. Chem. (2002) [Pubmed]
  7. The effect of hypoxia on endogenous corneal epithelial eicosanoids. Mieyal, P.A., Bonazzi, A., Jiang, H., Dunn, M.W., Schwartzman, M.L. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  8. Effects of COX-2 inhibitors on aortic prostacyclin production in cholesterol-fed rabbits. Wong, E., Huang, J.Q., Tagari, P., Riendeau, D. Atherosclerosis (2001) [Pubmed]
  9. Early inflammatory arthritis in the rabbit: the influence of intraarticular and systemic corticosteroids on mRNA levels in connective tissues of the knee. Kydd, A.S., Reno, C.R., Tsao, H.W., Hart, D.A. J. Rheumatol. (2007) [Pubmed]
  10. Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy. Gamache, D.A., Graff, G., Brady, M.T., Spellman, J.M., Yanni, J.M. Inflammation (2000) [Pubmed]
  11. Atorvastatin reduces the expression of cyclooxygenase-2 in a rabbit model of atherosclerosis and in cultured vascular smooth muscle cells. Hernández-Presa, M.A., Martín-Ventura, J.L., Ortego, M., Gómez-Hernández, A., Tuñón, J., Hernández-Vargas, P., Blanco-Colio, L.M., Mas, S., Aparicio, C., Ortega, L., Vivanco, F., Gerique, J.G., Díaz, C., Hernández, G., Egido, J. Atherosclerosis (2002) [Pubmed]
  12. Cyclooxygenase- and lipoxygenase-dependent relaxation to arachidonic acid in rabbit small mesenteric arteries. Zhang, D.X., Gauthier, K.M., Chawengsub, Y., Holmes, B.B., Campbell, W.B. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  13. Hormonal regulation of PGE2 and COX-2 production in rabbit uterine cervical fibroblasts. Sato, T., Michizu, H., Hashizume, K., Ito, A. J. Appl. Physiol. (2001) [Pubmed]
  14. The lipoxygenase-cyclooxygenase inhibitor licofelone prevents thromboxane A2-mediated cardiovascular derangement triggered by the inflammatory peptide fMLP in the rabbit. Rotondo, S., Dell'elba, G., Manarini, S., Cerletti, C., Evangelista, V. Eur. J. Pharmacol. (2006) [Pubmed]
  15. Selective targeting of cyclooxygenase-2 reveals its role in renal medullary interstitial cell survival. Hao, C.M., Kömhoff, M., Guan, Y., Redha, R., Breyer, M.D. Am. J. Physiol. (1999) [Pubmed]
  16. Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: new pharmacological opportunities due to related binding site recognition. Weber, A., Casini, A., Heine, A., Kuhn, D., Supuran, C.T., Scozzafava, A., Klebe, G. J. Med. Chem. (2004) [Pubmed]
  17. Isoflurane produces delayed preconditioning against myocardial ischemia and reperfusion injury: role of cyclooxygenase-2. Tanaka, K., Ludwig, L.M., Krolikowski, J.G., Alcindor, D., Pratt, P.F., Kersten, J.R., Pagel, P.S., Warltier, D.C. Anesthesiology (2004) [Pubmed]
  18. Augmented myocardial ischaemia by nicotine--mechanisms and their possible significance. Schrör, K., Zimmermann, K.C., Tannhäuser, R. Br. J. Pharmacol. (1998) [Pubmed]
  19. Effects of intravenous administration of FR122047 (a selective cyclooxygenase 1 inhibitor) and FR188582 (a selective cyclooxygenase 2 inhibitor) on prostaglandin-E2-induced aqueous flare elevation in pigmented rabbits. Abe, T., Hayasaka, Y., Zhang, X.Y., Hayasaka, S. Ophthalmic Res. (2004) [Pubmed]
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