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Gene Review

Alox15  -  arachidonate 15-lipoxygenase

Rattus norvegicus

Synonyms: 12-LOX, 12/15-lipoxygenase, 15-LOX, Alox12, Alox12l, ...
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Disease relevance of Alox15


Psychiatry related information on Alox15

  • The difference in sensitivity was not due to a difference in 12-LOX activity but rather appeared to be related to the presence of stronger antioxidant defense mechanisms in mature OLs [4].

High impact information on Alox15

  • Using immature cortical neurons and a clonal nerve cell line, it is shown that a decrease in GSH triggers the activation of neuronal 12-lipoxygenase (12-LOX), which leads to the production of peroxides, the influx of Ca2+, and ultimately to cell death [5].
  • W256 cells transfected with 12-LOX-specific antisense oligonucleotide or antisense oligonucleotides directed to conserved regions of LOXs underwent time- and dose-dependent apoptosis [1].
  • In addition we show that if GSH synthesis inhibition persists for up to 4 days without any additional treatment, it will induce a cell death process that also depends on 12-LOX, GC, and PKG activation [2].
  • Here we demonstrate that arachidonic acid (AA) metabolism through the 12-lipoxygenase (12-LOX) pathway is also central for this GSH-NO interaction [2].
  • Overexpression of 12-LOX enhanced the surface expression and focal adhesion localization of integrin alphavbeta5, while not affecting other integrins [6].

Chemical compound and disease context of Alox15


Biological context of Alox15


Anatomical context of Alox15


Associations of Alox15 with chemical compounds

  • Incubation of pineal homogenates with exogenous melatonin partially inhibited 12-LOX activity [9].
  • The reduction of 12-HETE levels during the dark phase and after isoproterenol injection was accompanied by decreases in 12-LOX mRNA and protein levels [9].
  • Blocking 12-LOX with AA-861 effectively inhibited the accumulation of reactive oxygen species (ROS) induced by cystine deprivation [4].
  • These data indicate zaltoprofen may produce its analgesic effects through the inhibition of bradykinin B2 receptor-mediated bradykinin responses of not only cyclooxygenases (COXs) but also bradykinin induced 12-LOX inhibitors [12].
  • Zaltoprofen also significantly inhibits bradykinin-induced 12-lipoxygenase (12-LOX) activity and the slow bradykinin-induced onset of substance P release from DRG neurons [12].

Regulatory relationships of Alox15


Other interactions of Alox15

  • These data suggest a cell death pathway triggered by peroxynitrite in which intracellular zinc release leads to activation of 12-LOX, ROS accumulation, p38 activation, and caspase-3 activation [3].
  • We researched the expression of COXs (COX-1 and COX-2) and LOXs (5-LOX and 12-LOX) in rat renal I/R injury [14].

Analytical, diagnostic and therapeutic context of Alox15


  1. Arachidonate lipoxygenases as essential regulators of cell survival and apoptosis. Tang, D.G., Chen, Y.Q., Honn, K.V. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  2. Nitric oxide triggers the toxicity due to glutathione depletion in midbrain cultures through 12-lipoxygenase. Canals, S., Casarejos, M.J., de Bernardo, S., Rodríguez-Martín, E., Mena, M.A. J. Biol. Chem. (2003) [Pubmed]
  3. Peroxynitrite-induced neuronal apoptosis is mediated by intracellular zinc release and 12-lipoxygenase activation. Zhang, Y., Wang, H., Li, J., Jimenez, D.A., Levitan, E.S., Aizenman, E., Rosenberg, P.A. J. Neurosci. (2004) [Pubmed]
  4. 12-Lipoxygenase plays a key role in cell death caused by glutathione depletion and arachidonic acid in rat oligodendrocytes. Wang, H., Li, J., Follett, P.L., Zhang, Y., Cotanche, D.A., Jensen, F.E., Volpe, J.J., Rosenberg, P.A. Eur. J. Neurosci. (2004) [Pubmed]
  5. A role for 12-lipoxygenase in nerve cell death caused by glutathione depletion. Li, Y., Maher, P., Schubert, D. Neuron (1997) [Pubmed]
  6. Overexpression of leukocyte-type 12-lipoxygenase promotes W256 tumor cell survival by enhancing alphavbeta5 expression. Pidgeon, G.P., Tang, K., Rice, R.L., Zacharek, A., Li, L., Taylor, J.D., Honn, K.V. Int. J. Cancer (2003) [Pubmed]
  7. 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]
  8. Renal oxygenases: differential contribution to vasoconstriction induced by ET-1 and ANG II. Oyekan, A., Balazy, M., McGiff, J.C. Am. J. Physiol. (1997) [Pubmed]
  9. Melatonin: an endogenous negative modulator of 12-lipoxygenation in the rat pineal gland. Zhang, H., Akbar, M., Kim, H.Y. Biochem. J. (1999) [Pubmed]
  10. The erythroid arachidonate 15-lipoxygenase in rat reticulocytes. Schewe, T., Kroschwald, P., Kroschwald, A., Ludwig, P., Kühn, H. Biomed. Biochim. Acta (1990) [Pubmed]
  11. Alterations of activities of cytosolic phospholipase A2 and arachidonic acid-metabolizing enzymes in di-(2-ethylhexyl)phthalate-induced testicular atrophy. Kim, H.S., Ishizuka, M., Kazusaka, A., Fujita, S. J. Vet. Med. Sci. (2004) [Pubmed]
  12. Zaltoprofen inhibits bradykinin-induced responses by blocking the activation of second messenger signaling cascades in rat dorsal root ganglion cells. Tang, H.B., Inoue, A., Oshita, K., Hirate, K., Nakata, Y. Neuropharmacology (2005) [Pubmed]
  13. Endothelin-1 stimulates arachidonate 15-lipoxygenase activity and oxygen radical formation in the rat distal lung. Nagase, T., Fukuchi, Y., Jo, C., Teramoto, S., Uejima, Y., Ishida, K., Shimizu, T., Orimo, H. Biochem. Biophys. Res. Commun. (1990) [Pubmed]
  14. The expression of cyclooxygenases and lipoxygenases in renal ischemia-reperfusion injury. Matsuyama, M., Nakatani, T., Hase, T., Kawahito, Y., Sano, H., Kawamura, M., Yoshimura, R. Transplant. Proc. (2004) [Pubmed]
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