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Gene Review

Alox5  -  arachidonate 5-lipoxygenase

Mus musculus

Synonyms: 5-LO, 5-LOX, 5-lipoxygenase, 5LO, 5LX, ...
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Disease relevance of Alox5

  • The 5-LO product inducing lipid body formation was not LTB4 but was 5(S)-hydroxyeicosatetraenoic acid [5(S)-HETE], which was active at 10-fold lower concentrations than PAF and was also inhibited by pertussis toxin but not by zileuton or WEB 2086 [1].
  • These 5LO(-/-) mice were unable to synthesize detectable levels of leukotrienes and were more resistant to lethal anaphylaxis induced by platelet-activating factor [2].
  • We found that 5-LO knockout mice that were treated with a COX inhibitor during allergic sensitization and challenge had significantly increased airway hyperresponsiveness (AHR) (p < 0.01) and airway eosinophilia (p < 0.01) compared with 5-LO knockout mice that were treated with vehicle [3].
  • We also demonstrated that the treatment of AA (1 mumol) and 5-LO metabolites including leukotriene B4 (LTB4) partly mimicked, though soybean LO-derived lipid hydroperoxide and prostaglandins did not, the priming effect evaluated by edema formation and leukocyte infiltration [4].
  • Chronic administration of butylated hydroxytoluene (BHT) to mice stimulates pulmonary inflammation characterized by vascular leakage and macrophage infiltration into the air spaces, increased PGE2 production, and translocation of 5-lipoxygenase (5-LO) from the cytosol to the particulate fraction [5].

Psychiatry related information on Alox5

  • METHODS: The following behavioral tests were used for behavioral characterization of 5LOX(-) mice: elevated plus-maze, marble burying, locomotor activity, rota-road, and the spontaneous alternations in T-maze [6].

High impact information on Alox5


Chemical compound and disease context of Alox5


Biological context of Alox5


Anatomical context of Alox5

  • Mechanisms of platelet-activating factor-induced lipid body formation: requisite roles for 5-lipoxygenase and de novo protein synthesis in the compartmentalization of neutrophil lipids [1].
  • Corroborating the dependency of PAF-induced lipid body formation on 5-LO, PMN and macrophages from wild-type mice, but not from 5-LO genetically deficient mice, formed lipid bodies on exposure to PAF both in vitro and in vivo within the pleural cavity [1].
  • Overexpression of BLTR in leukocytes dramatically increased PMN trafficking to skin microabscesses and lungs after ischemia-reperfusion, whereas mice deficient in 5-lipoxygenase (5-LO) showed diminished PMN accumulation in reperfused lungs [18].
  • Also, in BLTR transgenic mice, 5-LO expression and product formation were selectively increased in exudates, demonstrating that receptor overexpression amplifies proinflammatory circuits [18].
  • Consistent with these data, transfer of autoreactive T cells from B6 mice to 5-lipoxygenase-deficient (5-LO-/-) mice, which have a functional defect in LTB4 expression, also failed to induce uveitis in the recipient mice [19].

Associations of Alox5 with chemical compounds

  • The intensity of an acute inflammatory response induced by arachidonic acid was similar in 5LO(-/-) mice and controls [2].
  • Dietary celecoxib limited macrophage infiltration, abrogated PGE2 production and reduced particulate 5-LO content [5].
  • It was found that 1mM N6,2-O-dibutyryladenosine 3:5-cyclic monophosphate (dbcAMP) significantly increased the 5-lipoxygenase metabolites, 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and 5-hydroxyeicosatetraenoic acid (5-HETE) [16].
  • We have studied the effect of 5- O-demethylnobiletin ( 1) on both the inflammation of mouse ears induced by repeated application of 12- O-tetradecanoylphorbol 13-acetate (TPA) and the acute mouse paw oedemas induced by carrageenan and phospholipase A (2) (PLA (2)), and determined its activity on 5-lipoxygenase (5-LOX) and elastase release/activity [20].
  • These results indicate that norathyriol inhibits the formation of PGs and LTs in neutrophils probably through direct blockade of COX and 5-LO activities [21].

Regulatory relationships of Alox5

  • It has long been proposed that the inhibition of the 5-LO could enhance the COX pathway leading to an increased PG generation [22].
  • These findings indicate the potential role of COX-2 inhibitors and also their combination with the 5-LOX inhibitor in kainic acid induced excitotoxicity and oxidative damage by virtue of their antioxidant effect and suggest the need for the development of dual inhibitors for the treatment of neuronal excitotoxicity [23].
  • Prostaglandins inhibit 5-lipoxygenase-activating protein expression and leukotriene B4 production from dendritic cells via an IL-10-dependent mechanism [24].
  • The addition of sPLA2 to Ag-stimulated mast cells increases the synthesis of 5-LO products [25].
  • A cyclooxygenase inhibitor, a 5-lipoxygenase-activating protein inhibitor and a PAF receptor antagonist did not affect the scratching behavior [26].

Other interactions of Alox5


Analytical, diagnostic and therapeutic context of Alox5


  1. Mechanisms of platelet-activating factor-induced lipid body formation: requisite roles for 5-lipoxygenase and de novo protein synthesis in the compartmentalization of neutrophil lipids. Bozza, P.T., Payne, J.L., Goulet, J.L., Weller, P.F. J. Exp. Med. (1996) [Pubmed]
  2. Altered inflammatory responses in leukotriene-deficient mice. Goulet, J.L., Snouwaert, J.N., Latour, A.M., Coffman, T.M., Koller, B.H. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  3. Allergen-induced airway hyperresponsiveness mediated by cyclooxygenase inhibition is not dependent on 5-lipoxygenase or IL-5, but is IL-13 dependent. Peebles, R.S., Hashimoto, K., Sheller, J.R., Moore, M.L., Morrow, J.D., Ji, S., Elias, J.A., Goleniewska, K., O'neal, J., Mitchell, D.B., Graham, B.S., Zhou, W. J. Immunol. (2005) [Pubmed]
  4. Arachidonic acid cascade inhibitors modulate phorbol ester-induced oxidative stress in female ICR mouse skin: differential roles of 5-lipoxygenase and cyclooxygenase-2 in leukocyte infiltration and activation. Nakamura, Y., Kozuka, M., Naniwa, K., Takabayashi, S., Torikai, K., Hayashi, R., Sato, T., Ohigashi, H., Osawa, T. Free Radic. Biol. Med. (2003) [Pubmed]
  5. Celecoxib reduces pulmonary inflammation but not lung tumorigenesis in mice. Kisley, L.R., Barrett, B.S., Dwyer-Nield, L.D., Bauer, A.K., Thompson, D.C., Malkinson, A.M. Carcinogenesis (2002) [Pubmed]
  6. 5-lipoxygenase (5LOX)-deficient mice express reduced anxiety-like behavior. Uz, T., Dimitrijevic, N., Tueting, P., Manev, H. Restorative neurology and neuroscience. (2002) [Pubmed]
  7. Integrating genotypic and expression data in a segregating mouse population to identify 5-lipoxygenase as a susceptibility gene for obesity and bone traits. Mehrabian, M., Allayee, H., Stockton, J., Lum, P.Y., Drake, T.A., Castellani, L.W., Suh, M., Armour, C., Edwards, S., Lamb, J., Lusis, A.J., Schadt, E.E. Nat. Genet. (2005) [Pubmed]
  8. Epidermal growth factor activates calcium channels by phospholipase A2/5-lipoxygenase-mediated leukotriene C4 production. Peppelenbosch, M.P., Tertoolen, L.G., den Hertog, J., de Laat, S.W. Cell (1992) [Pubmed]
  9. The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm. Zhao, L., Moos, M.P., Gräbner, R., Pédrono, F., Fan, J., Kaiser, B., John, N., Schmidt, S., Spanbroek, R., Lötzer, K., Huang, L., Cui, J., Rader, D.J., Evans, J.F., Habenicht, A.J., Funk, C.D. Nat. Med. (2004) [Pubmed]
  10. Thioglycollate peritonitis in mice lacking C5, 5-lipoxygenase, or p47(phox): complement, leukotrienes, and reactive oxidants in acute inflammation. Segal, B.H., Kuhns, D.B., Ding, L., Gallin, J.I., Holland, S.M. J. Leukoc. Biol. (2002) [Pubmed]
  11. Is there a role for the macrophage 5-lipoxygenase pathway in aortic aneurysm development in apolipoprotein e-deficient mice? Funk, C.D., Cao, R.Y., Zhao, L., Habenicht, A.J. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  12. Distinct Effects of Annexin A7 and p53 on Arachidonate Lipoxygenation in Prostate Cancer Cells Involve 5-Lipoxygenase Transcription. Torosyan, Y., Dobi, A., Naga, S., Mezhevaya, K., Glasman, M., Norris, C., Jiang, G., Mueller, G., Pollard, H., Srivastava, M. Cancer Res. (2006) [Pubmed]
  13. 5-Lipoxygenase, a marker for early pancreatic intraepithelial neoplastic lesions. Hennig, R., Grippo, P., Ding, X.Z., Rao, S.M., Buchler, M.W., Friess, H., Talamonti, M.S., Bell, R.H., Adrian, T.E. Cancer Res. (2005) [Pubmed]
  14. Cloning and functional analysis of the mouse 5-lipoxygenase promoter. Silverman, E.S., Le, L., Baron, R.M., Hallock, A., Hjoberg, J., Shikanai, T., Storm van's Gravesande, K., Auron, P.E., Lu, W. Am. J. Respir. Cell Mol. Biol. (2002) [Pubmed]
  15. 5-lipoxygenase and cyclooxygenase regulate wound closure in NIH/3T3 fibroblast monolayers. Green, J.A., Stockton, R.A., Johnson, C., Jacobson, B.S. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  16. Involvement of 5-lipoxygenase metabolites of arachidonic acid in cyclic AMP-stimulated steroidogenesis and steroidogenic acute regulatory protein gene expression. Wang, X.J., Dyson, M.T., Jo, Y., Eubank, D.W., Stocco, D.M. J. Steroid Biochem. Mol. Biol. (2003) [Pubmed]
  17. Immunoregulatory properties of novel specific inhibitors of 5-lipoxygenase. Liu, D.S., Liew, F.Y., Rhodes, J. Immunopharmacology (1989) [Pubmed]
  18. Leukotriene B4 receptor transgenic mice reveal novel protective roles for lipoxins and aspirin-triggered lipoxins in reperfusion. Chiang, N., Gronert, K., Clish, C.B., O'Brien, J.A., Freeman, M.W., Serhan, C.N. J. Clin. Invest. (1999) [Pubmed]
  19. Blockade of the interaction of leukotriene b4 with its receptor prevents development of autoimmune uveitis. Liao, T., Ke, Y., Shao, W.H., Haribabu, B., Kaplan, H.J., Sun, D., Shao, H. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  20. Anti-inflammatory activity of 5-O-demethylnobiletin, a polymethoxyflavone isolated from Sideritis tragoriganum. Bas, E., Recio, M.C., Giner, R.M., Máñez, S., Cerdá-Nicolás, M., Ríos, J.L. Planta Med. (2006) [Pubmed]
  21. Inhibition of the arachidonic acid cascade by norathyriol via blockade of cyclooxygenase and lipoxygenase activity in neutrophils. Hsu, M.F., Lin, C.N., Lu, M.C., Wang, J.P. Naunyn Schmiedebergs Arch. Pharmacol. (2004) [Pubmed]
  22. Up-regulation of prostaglandin biosynthesis by leukotriene C4 in elicited mice peritoneal macrophages activated with lipopolysaccharide/interferon-{gamma}. Rossi, A., Acquaviva, A.M., Iuliano, F., Di Paola, R., Cuzzocrea, S., Sautebin, L. J. Leukoc. Biol. (2005) [Pubmed]
  23. Co-Administration of Acetyl-11-Keto-beta-Boswellic Acid, a Specific 5-Lipoxygenase Inhibitor, Potentiates the Protective Effect of COX-2 Inhibitors in Kainic Acid-Induced Neurotoxicity in Mice. Bishnoi, M., Patil, C.S., Kumar, A., Kulkarni, S.K. Pharmacology (2007) [Pubmed]
  24. Prostaglandins inhibit 5-lipoxygenase-activating protein expression and leukotriene B4 production from dendritic cells via an IL-10-dependent mechanism. Harizi, H., Juzan, M., Moreau, J.F., Gualde, N. J. Immunol. (2003) [Pubmed]
  25. Evidence that secretory phospholipase A2 plays a role in arachidonic acid release and eicosanoid biosynthesis by mast cells. Fonteh, A.N., Bass, D.A., Marshall, L.A., Seeds, M., Samet, J.M., Chilton, F.H. J. Immunol. (1994) [Pubmed]
  26. Involvement of unique mechanisms in the induction of scratching behavior in BALB/c mice by compound 48/80. Inagaki, N., Igeta, K., Kim, J.F., Nagao, M., Shiraishi, N., Nakamura, N., Nagai, H. Eur. J. Pharmacol. (2002) [Pubmed]
  27. Deficiency of 5-lipoxygenase abolishes sex-related survival differences in MRL-lpr/lpr mice. Goulet, J.L., Griffiths, R.C., Ruiz, P., Spurney, R.F., Pisetsky, D.S., Koller, B.H., Coffman, T.M. J. Immunol. (1999) [Pubmed]
  28. Synthesis of sterols and 5-lipoxygenase products are required for the G1-S phase transition of interleukin-2-dependent lymphocyte proliferation. Hata, S., Sugama, K., You-Li, Z., Hatanaka, M., Namba, Y., Hanaoka, M. Microbiol. Immunol. (1987) [Pubmed]
  29. Naturally occurring biflavonoid, ochnaflavone, inhibits cyclooxygenases-2 and 5-lipoxygenase in mouse bone marrow-derived mast cells. Son, M.J., Moon, T.C., Lee, E.K., Son, K.H., Kim, H.P., Kang, S.S., Son, J.K., Lee, S.H., Chang, H.W. Arch. Pharm. Res. (2006) [Pubmed]
  30. Phorbol ester-induced dermal inflammation in mice: evaluation of inhibitors of 5-lipoxygenase and antagonists of leukotriene B4 receptor. Rao, T.S., Yu, S.S., Djuric, S.W., Isakson, P.C. Journal of lipid mediators and cell signalling. (1994) [Pubmed]
  31. The expression of brain cyclooxygenase-2 is down-regulated in the cytosolic phospholipase A2 knockout mouse. Bosetti, F., Weerasinghe, G.R. J. Neurochem. (2003) [Pubmed]
  32. Deficiency of 5-lipoxygenase accelerates renal allograft rejection in mice. Goulet, J.L., Griffiths, R.C., Ruiz, P., Mannon, R.B., Flannery, P., Platt, J.L., Koller, B.H., Coffman, T.M. J. Immunol. (2001) [Pubmed]
  33. cDNA cloning, expression, mutagenesis, intracellular localization, and gene chromosomal assignment of mouse 5-lipoxygenase. Chen, X.S., Naumann, T.A., Kurre, U., Jenkins, N.A., Copeland, N.G., Funk, C.D. J. Biol. Chem. (1995) [Pubmed]
  34. Opposing and hierarchical roles of leukotrienes in local innate immune versus vascular responses in a model of sepsis. Benjamim, C.F., Canetti, C., Cunha, F.Q., Kunkel, S.L., Peters-Golden, M. J. Immunol. (2005) [Pubmed]
  35. 5-lipoxygenase knockout mice exhibit a resistance to splanchnic artery occlusion shock. Cuzzocrea, S., Rossi, A., Serraino, I., Di Paola, R., Dugo, L., Genovese, T., Caputi, A.P., Sautebin, L. Shock (2003) [Pubmed]
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