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Gene Review

Alox5  -  arachidonate 5-lipoxygenase

Rattus norvegicus

Synonyms: 5-LO, 5-lipoxygenase, Arachidonate 5-lipoxygenase
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Disease relevance of Alox5


High impact information on Alox5

  • Furthermore, opioid inhibition of GABAergic synaptic transmission is potentiated by inhibitors of the enzymes cyclooxygenase and 5-lipoxygenase, presumably because more arachidonic acid is available for conversion to 12-lipoxygenase products [5].
  • Recently a compound, MK-886, has been described that blocks the synthesis of leukotrienes in intact activated leukocytes, but has little or no effect on enzymes involved in leukotriene synthesis, including 5-lipoxygenase, in cell-free systems [6].
  • Osteosarcoma cells transfected with 5-LO express active enzyme in broken cell preparations, but no leukotriene metabolites are produced by these cells when stimulated with the calcium ionophore A23187, indicating that an additional component is necessary for cellular 5-LO activity [7].
  • The initial enzymatic step in the formation of leukotrienes is the oxidation of arachidonic acid by 5-lipoxygenase (5-LO) to leukotriene A4 [7].
  • A new class of indole leukotriene inhibitor has been described that inhibits the formation of cellular leukotrienes but has no direct inhibitory effect on soluble 5-LO activity [7].

Chemical compound and disease context of Alox5


Biological context of Alox5


Anatomical context of Alox5


Associations of Alox5 with chemical compounds

  • In this group of compounds, inhibition of both 5-LOX and 15-LOX was dependent upon the length of the alkyl substituent with the hex-1-ene compound 9c having a n-butyl substituent exhibiting potent inhibition of both 5-LOX (IC50=0.3 microM) and 15-LOX (IC50=0.8 microM) relative to the inactive (IC50>10 microM) Et and n-heptyl analogs [19].
  • Interaction between nitric oxide, reactive oxygen intermediates, and peroxynitrite in the regulation of 5-lipoxygenase metabolism [20].
  • Hearts were harvested and analyzed for myocardial lipoxin-A4 and 15-epi-LXA4 levels and for COX-2 and 5-lipoxygenase protein expression [21].
  • In experiment 2, rats received water; PIO 10 mg x kg(-1) x d(-1)+ATV 10 mg x kg(-1) x d(-1); PIO+ATV and valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor; PIO+ATV and zileuton, a selective 5-lipoxygenase inhibitor; or zileuton alone [21].
  • 5-Lipoxygenase is involved in the angiotensin II-induced NAD(P)H-oxidase activation [22].

Regulatory relationships of Alox5


Other interactions of Alox5

  • The increased leukotriene secretion of sPM in response to ovalbumin challenge may be favoured by this increased expression of cPLA2, 5-LO and FLAP that, however, is not able to lead to modifications of macrophage AA metabolism in any circumstance [16].
  • The ability of iPLA2 inhibitors to increase AMPA receptor-mediated currents was also reproduced by MK-866, an inhibitor recognized to interfere with the generation of 5-lipoxygenase by-products of AA [28].
  • Because NDGA could abrogate the LPS-induced activation of NFkappaB, while MK886 had no effect on it, LO-mediated inhibition of iNOS gene induction by LPS may involve an NFkappaB-dependent or -independent (by 5-LO) pathway [29].
  • This effect was inhibited by indomethacin (10microM) and ZM230487 (1microM), selective inhibitors of cyclooxygenase and of 5-lipoxygenase, respectively [30].
  • The results demonstrate the presence of a GnRH-activatable 5-lipoxygenase pathway in anterior pituitary cells and provide strong support for the hypothesis that LTs play a role in LH release in the GnRH signaling pathway [23].

Analytical, diagnostic and therapeutic context of Alox5


  1. Effect of 5-lipoxygenase on the development of pulmonary hypertension in rats. Jones, J.E., Walker, J.L., Song, Y., Weiss, N., Cardoso, W.V., Tuder, R.M., Loscalzo, J., Zhang, Y.Y. Am. J. Physiol. Heart Circ. Physiol. (2004) [Pubmed]
  2. 5-lipoxygenase expression and activity in aorta from streptozotocin-induced diabetic rats. Hardy, G., Vergnaud, S., Lunardi, J., Peoc'h, M., Bessard, G., Stanke-Labesque, F. Prostaglandins Other Lipid Mediat. (2005) [Pubmed]
  3. Prolonged exposure to lipopolysaccharide inhibits macrophage 5-lipoxygenase metabolism via induction of nitric oxide synthesis. Coffey, M.J., Phare, S.M., Peters-Golden, M. J. Immunol. (2000) [Pubmed]
  4. Acute effects of the cys-leukotriene-1 receptor antagonist, montelukast, on experimental colitis in rats. Holma, R., Salmenperä, P., Riutta, A., Virtanen, I., Korpela, R., Vapaatalo, H. Eur. J. Pharmacol. (2001) [Pubmed]
  5. How opioids inhibit GABA-mediated neurotransmission. Vaughan, C.W., Ingram, S.L., Connor, M.A., Christie, M.J. Nature (1997) [Pubmed]
  6. Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis. Dixon, R.A., Diehl, R.E., Opas, E., Rands, E., Vickers, P.J., Evans, J.F., Gillard, J.W., Miller, D.K. Nature (1990) [Pubmed]
  7. Identification and isolation of a membrane protein necessary for leukotriene production. Miller, D.K., Gillard, J.W., Vickers, P.J., Sadowski, S., Léveillé, C., Mancini, J.A., Charleson, P., Dixon, R.A., Ford-Hutchinson, A.W., Fortin, R. Nature (1990) [Pubmed]
  8. Effects of dual inhibitor of cyclooxygenase and 5-lipoxygenase on acute necrotizing pancreatitis in rats. Kalyoncu, N.I., Alhan, E., Ercin, C., Kural, B.V. Hepatogastroenterology (2006) [Pubmed]
  9. Exacerbation of experimental colitis by nonsteroidal anti-inflammatory drugs is not related to elevated leukotriene B4 synthesis. Wallace, J.L., Keenan, C.M., Gale, D., Shoupe, T.S. Gastroenterology (1992) [Pubmed]
  10. The role of leukotriene B4 in Clostridium difficile toxin A-induced ileitis in rats. McVey, D.C., Vigna, S.R. Gastroenterology (2005) [Pubmed]
  11. Inhibition of leukotriene synthesis markedly accelerates healing in a rat model of inflammatory bowel disease. Wallace, J.L., MacNaughton, W.K., Morris, G.P., Beck, P.L. Gastroenterology (1989) [Pubmed]
  12. AMPA receptor phosphorylation is selectively regulated by constitutive phospholipase A(2) and 5-lipoxygenase activities. Ménard, C., Valastro, B., Martel, M.A., Chartier, E., Marineau, A., Baudry, M., Massicotte, G. Hippocampus. (2005) [Pubmed]
  13. Isolation and characterization of a cDNA clone encoding rat 5-lipoxygenase. Balcarek, J.M., Theisen, T.W., Cook, M.N., Varrichio, A., Hwang, S.M., Strohsacker, M.W., Crooke, S.T. J. Biol. Chem. (1988) [Pubmed]
  14. Down-regulation of 5-lipoxygenase activity and leukotriene production by prolonged exposure to lipopolysaccharide. Brock, T.G. Adv. Exp. Med. Biol. (2002) [Pubmed]
  15. Minocycline protects PC12 cells against NMDA-induced injury via inhibiting 5-lipoxygenase activation. Song, Y., Wei, E.Q., Zhang, W.P., Ge, Q.F., Liu, J.R., Wang, M.L., Huang, X.J., Hu, X., Chen, Z. Brain Res. (2006) [Pubmed]
  16. Increased expression of cytosolic phospholipase A2, 5-lipoxygenase and 5-lipoxygenase-activating protein in rat peritoneal macrophages during ovalbumin-induced sensitization. Escoubet-Lozach, L., M'Rini, C., Rey, A., Béraud, M., Lepert, J.C., Courtade, M., Frisach, M.F., Pipy, B. Clin. Exp. Allergy (2001) [Pubmed]
  17. Hyperoxia increases protein mass of 5-lipoxygenase and its activating protein, flap, and leukotriene B(4) output in newborn rat lungs. Hosford, G.E., Koyanagi, K.S., Leung, W.I., Olson, D.M. Exp. Lung Res. (2002) [Pubmed]
  18. Mechanisms of the influence of magnolol on eicosanoid metabolism in neutrophils. Hsu, M.F., Lu, M.C., Tsao, L.T., Kuan, Y.H., Chen, C.C., Wang, J.P. Biochem. Pharmacol. (2004) [Pubmed]
  19. Synthesis and biological evaluation of acyclic triaryl (Z)-olefins possessing a 3,5-di-tert-butyl-4-hydroxyphenyl pharmacophore: dual inhibitors of cyclooxygenases and lipoxygenases. Moreau, A., Rao, P.N., Knaus, E.E. Bioorg. Med. Chem. (2006) [Pubmed]
  20. Interaction between nitric oxide, reactive oxygen intermediates, and peroxynitrite in the regulation of 5-lipoxygenase metabolism. Coffey, M.J., Phare, S.M., Peters-Golden, M. Biochim. Biophys. Acta (2002) [Pubmed]
  21. Augmentation of myocardial production of 15-epi-lipoxin-a4 by pioglitazone and atorvastatin in the rat. Birnbaum, Y., Ye, Y., Lin, Y., Freeberg, S.Y., Nishi, S.P., Martinez, J.D., Huang, M.H., Uretsky, B.F., Perez-Polo, J.R. Circulation (2006) [Pubmed]
  22. 5-Lipoxygenase is involved in the angiotensin II-induced NAD(P)H-oxidase activation. Luchtefeld, M., Drexler, H., Schieffer, B. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  23. Production of leukotrienes in gonadotropin-releasing hormone-stimulated pituitary cells: potential role in luteinizing hormone release. Kiesel, L., Przylipiak, A.F., Habenicht, A.J., Przylipiak, M.S., Runnebaum, B. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  24. Induction of interleukin-6 release by interleukin-1 in rat anterior pituitary cells in vitro: evidence for an eicosanoid-dependent mechanism. Spangelo, B.L., Jarvis, W.D., Judd, A.M., MacLeod, R.M. Endocrinology (1991) [Pubmed]
  25. Suppression of leukotriene formation in RBL-2H3 cells that overexpressed phospholipid hydroperoxide glutathione peroxidase. Imai, H., Narashima, K., Arai, M., Sakamoto, H., Chiba, N., Nakagawa, Y. J. Biol. Chem. (1998) [Pubmed]
  26. Reduced release of leukotrienes B4 and C4 from alveolar macrophages of rats with silicosis. Mohr, C., Davis, G.S., Graebner, C., Amann, S., Hemenway, D.R., Gemsa, D. Am. J. Respir. Cell Mol. Biol. (1992) [Pubmed]
  27. Nordihydroguaiaretic acid protects hippocampal neurons against amyloid beta-peptide toxicity, and attenuates free radical and calcium accumulation. Goodman, Y., Steiner, M.R., Steiner, S.M., Mattson, M.P. Brain Res. (1994) [Pubmed]
  28. Postsynaptic injection of calcium-independent phospholipase A2 inhibitors selectively increases AMPA receptor-mediated synaptic transmission. St-Gelais, F., Ménard, C., Congar, P., Trudeau, L.E., Massicotte, G. Hippocampus. (2004) [Pubmed]
  29. Involvement of phospholipase A2 and lipoxygenase in lipopolysaccharide-induced inducible nitric oxide synthase expression in glial cells. Won, J.S., Im, Y.B., Khan, M., Singh, A.K., Singh, I. Glia (2005) [Pubmed]
  30. Vascular effects of 7-epiclusianone, a prenylated benzophenone from Rheedia gardneriana, on the rat aorta. Cruz, A.J., Lemos, V.S., dos Santos, M.H., Nagem, T.J., Cortes, S.F. Phytomedicine (2006) [Pubmed]
  31. Mesangial cell immune injury. Hemodynamic role of leukocyte- and platelet-derived eicosanoids. Bresnahan, B.A., Wu, S., Fenoy, F.J., Roman, R.J., Lianos, E.A. J. Clin. Invest. (1992) [Pubmed]
  32. Hepatocyte-derived cysteinyl leukotrienes modulate vascular tone in experimental cirrhosis. Titos, E., Clària, J., Bataller, R., Bosch-Marcé, M., Ginès, P., Jiménez, W., Arroyo, V., Rivera, F., Rodés, J. Gastroenterology (2000) [Pubmed]
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