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Gene Review

Alox15  -  arachidonate 15-lipoxygenase

Mus musculus

Synonyms: 12-LO, 12-LOX, 12/15-LO, 12/15-lipoxygenase, 15-LOX, ...
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Disease relevance of Alox15

  • Here, we provide in vivo evidence for the role of 12/15-lipoxygenase in atherogenesis and demonstrate diminished plasma IgG autoantibodies to oxidized LDL epitopes in 12/15-lipoxygenase knockout mice crossbred with atherosclerosis-prone apo E-deficient mice (apo E-/-/L-12LO-/-) [1].
  • At the acute stage of infection, when granuloma formation is usually maximal, 5-LO deficient mice developed smaller granulomas around liver-deposited schistosome eggs compared with wild type or 12-LO deficient mice [2].
  • In this report we characterize e-12LO, which was overexpressed in the baculovirus/insect cell expression system [3].
  • 12-lipoxygenase (12-lipoxygenase) (12-LOX) was recruited to glycosphingolipid-enriched microdomains (GEM) in a GM3-dependent manner during oxidative glutamate toxicity [4].
  • Arachidonic acid is metabolized by 12-LOX to 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], and this biologically active metabolite is involved in prostate cancer progression by modulating cell proliferation in multiple cancer-related pathways inducing angiogenesis and metastasis [5].

Psychiatry related information on Alox15


High impact information on Alox15


Biological context of Alox15

  • Collectively, these results identify a novel action for the mouse 12/15-LOX (Alox15) and its products, LXA(4) and NPD1, in wound healing that is distinct from their well established anti-inflammatory properties [8].
  • Through combined genetic and genomic approaches, we identified the lipoxygenase gene Alox15 as a negative regulator of peak bone mineral density in mice [9].
  • Crossbreeding experiments with Alox15 knockout mice confirmed that 12/15-lipoxygenase plays a role in skeletal development [9].
  • The epidermal lipoxygenase gene (Aloxe) resides on mouse chromosome 11 closely linked with the two 12-lipoxygenase genes (Alox12p and Alox12l) [10].
  • As one example, analysis of a murine genetic model of osteoporosis demonstrated that genetic variation within the 15-lipoxygenase (Alox15) gene affected peak bone mass, and that treatment with inhibitors of this enzyme improved bone mass and quality in rodent models [11].

Anatomical context of Alox15


Associations of Alox15 with chemical compounds

  • OBJECTIVES: We have utilized mice with a disruption of the "leukocyte-type" 12-lipoxygenase gene (12-LO-/- mice) to examine a variety of general behavioral responses as well as several specific responses to morphine and cocaine [6].
  • Although the antipsoriatic drug, anthralin, predominantly inhibited epidermal 12-LO, the novel derivatives were more selective 5-LO inhibitors [13].
  • By contrast, 12-LO, 15-LO, phosphodiesterase activity and histamine release from mast cells and basophils were unaffected by Wy-48,252 [14].
  • Moreover, 5,8,11-eicosatriynoic acid (ETI) which inhibits 5- and 12-LO, and 5, 8, 11, 14-eicosatetraynoic acid (ETYA) which inhibits all known LOs did not affect B-lymphocyte proliferation [15].
  • Previously published investigations with the nonspecific 5-LO (EC and 12-LO (EC inhibitors such as nordihydroguaiaretic acid (NDGA) and 6,7-dihydroxycoumarin (Esculetin), are misleading in that they suggest lymphocyte LO activity is required for activation and differentiation of these cells [15].

Regulatory relationships of Alox15


Other interactions of Alox15

  • Addition of 12-HETE to 12-LO knockout islet cells produced a statistically significant rise in PGE2 production [16].
  • Inhibition of either COX-2 or 12-LO can prevent cytokine-induced pancreatic beta-cell dysfunction as defined by inhibition of glucose-stimulated insulin secretion [16].
  • GnRH nearly doubled the release of 12-hydroeicosatetraenoic acid, a product of the 12-LO enzyme, within 10 min [19].
  • LbetaT2 cells represent a potential model to further study the involvement of 12-LO in GnRH receptor signaling [19].
  • In summary, diabetes in vivo and exposure of podocytes to HG in vitro stimulated 12-LO, p38 MAPK, and collagen alpha5(IV) mRNA and (activated) protein [20].

Analytical, diagnostic and therapeutic context of Alox15


  1. Disruption of the 12/15-lipoxygenase gene diminishes atherosclerosis in apo E-deficient mice. Cyrus, T., Witztum, J.L., Rader, D.J., Tangirala, R., Fazio, S., Linton, M.F., Funk, C.D. J. Clin. Invest. (1999) [Pubmed]
  2. Mice deficient for 5-lipoxygenase, but not leukocyte-type 12-lipoxygenase, display altered immune responses during infection with Schistosoma mansoni. Secor, W.E., Powell, M.R., Morgan, J., Wynn, T.A., Funk, C.D. Prostaglandins Other Lipid Mediat. (1998) [Pubmed]
  3. Characterization of the murine epidermal 12/15-lipoxygenase. McDonnell, M., Davis, W., Li, H., Funk, C.D. Prostaglandins Other Lipid Mediat. (2001) [Pubmed]
  4. Ganglioside GM3 is involved in neuronal cell death. Sohn, H., Kim, Y.S., Kim, H.T., Kim, C.H., Cho, E.W., Kang, H.Y., Kim, N.S., Kim, C.H., Ryu, S.E., Lee, J.H., Ko, J.H. FASEB J. (2006) [Pubmed]
  5. Synthetic curcuminoids modulate the arachidonic acid metabolism of human platelet 12-lipoxygenase and reduce sprout formation of human endothelial cells. Jankun, J., Aleem, A.M., Malgorzewicz, S., Szkudlarek, M., Zavodszky, M.I., Dewitt, D.L., Feig, M., Selman, S.H., Skrzypczak-Jankun, E. Mol. Cancer Ther. (2006) [Pubmed]
  6. Augmented responses to morphine and cocaine in mice with a 12-lipoxygenase gene disruption. Walters, C.L., Wang, B.C., Godfrey, M., Sun, D., Funk, C.D., Blendy, J.A. Psychopharmacology (Berl.) (2003) [Pubmed]
  7. Resistance to type 1 diabetes induction in 12-lipoxygenase knockout mice. Bleich, D., Chen, S., Zipser, B., Sun, D., Funk, C.D., Nadler, J.L. J. Clin. Invest. (1999) [Pubmed]
  8. A role for the mouse 12/15-lipoxygenase pathway in promoting epithelial wound healing and host defense. Gronert, K., Maheshwari, N., Khan, N., Hassan, I.R., Dunn, M., Laniado Schwartzman, M. J. Biol. Chem. (2005) [Pubmed]
  9. Regulation of bone mass in mice by the lipoxygenase gene Alox15. Klein, R.F., Allard, J., Avnur, Z., Nikolcheva, T., Rotstein, D., Carlos, A.S., Shea, M., Waters, R.V., Belknap, J.K., Peltz, G., Orwoll, E.S. Science (2004) [Pubmed]
  10. Functional expression and cellular localization of a mouse epidermal lipoxygenase. Funk, C.D., Keeney, D.S., Oliw, E.H., Boeglin, W.E., Brash, A.R. J. Biol. Chem. (1996) [Pubmed]
  11. Understanding our drugs and our diseases. Guo, Y., Weller, P., Allard, J., Usuka, J., Masjedizadeh, M., Wu, S.Y., Fitch, B., Clark, D., Clark, J.D., Shafer, S., Wang, J., Liao, G., Peltz, G. Proceedings of the American Thoracic Society. (2006) [Pubmed]
  12. Disruption of 12/15-lipoxygenase expression in peritoneal macrophages. Enhanced utilization of the 5-lipoxygenase pathway and diminished oxidation of low density lipoprotein. Sun, D., Funk, C.D. J. Biol. Chem. (1996) [Pubmed]
  13. Novel 10-substituted antipsoriatic anthrones as inhibitors of epidermal 12-lipoxygenase and lipid peroxidation in membranes. Müller, K., Gawlik, I. Biochem. Pharmacol. (1995) [Pubmed]
  14. Wy-48,252 (1,1,1-trifluoro-N-[3-(2-quinolinylmethoxy)phenyl]membrane sulfonamide), an orally active leukotriene antagonist: effects on arachidonic acid metabolism in various inflammatory cells. Chang, J., Borgeat, P., Schleimer, R.P., Musser, J.H., Marshall, L.A., Hand, J.M. Eur. J. Pharmacol. (1988) [Pubmed]
  15. Reactive oxygen species and not lipoxygenase products are required for mouse B-lymphocyte activation and differentiation. Fedyk, E.R., Phipps, R.P. Int. J. Immunopharmacol. (1994) [Pubmed]
  16. Induction of cyclooxygenase-2 gene in pancreatic beta-cells by 12-lipoxygenase pathway product 12-hydroxyeicosatetraenoic acid. Han, X., Chen, S., Sun, Y., Nadler, J.L., Bleich, D. Mol. Endocrinol. (2002) [Pubmed]
  17. 12-lipoxygenase pathway increases aldosterone production, 3',5'-cyclic adenosine monophosphate response element-binding protein phosphorylation, and p38 mitogen-activated protein kinase activation in H295R human adrenocortical cells. Gu, J., Wen, Y., Mison, A., Nadler, J.L. Endocrinology (2003) [Pubmed]
  18. Evidence that increased 12-lipoxygenase expression impairs pancreatic beta cell function and viability. Prasad, K.M., Thimmalapura, P.R., Woode, E.A., Nadler, J.L. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  19. Gonadotropin-releasing hormone activates the 12-lipoxygenase pathway in the LbetaT2 gonadotrope cell line. Limor, R., Naor, Z., Weisinger, G., Naidich, M., Knoll, E., Sharon, O., Stern, N. Neuroendocrinology (2003) [Pubmed]
  20. Role of 12-lipoxygenase in the stimulation of p38 mitogen-activated protein kinase and collagen alpha5(IV) in experimental diabetic nephropathy and in glucose-stimulated podocytes. Kang, S.W., Natarajan, R., Shahed, A., Nast, C.C., LaPage, J., Mundel, P., Kashtan, C., Adler, S.G. J. Am. Soc. Nephrol. (2003) [Pubmed]
  21. Activation of 12-lipoxygenase in proinflammatory cytokine-mediated beta cell toxicity. Chen, M., Yang, Z.D., Smith, K.M., Carter, J.D., Nadler, J.L. Diabetologia (2005) [Pubmed]
  22. Role of 12-lipoxygenase in volatile anesthetic-induced delayed preconditioning in mice. Tsutsumi, Y.M., Patel, H.H., Huang, D., Roth, D.M. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
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