Genomes and Genes
Gene Symbol: Alox15
Description: arachidonate 15-lipoxygenase
Alias: 12-LOX, 15-LOX, Alox12, Alox12l, arachidonate 15-lipoxygenase, 12/15-LOX, 12/15-lipoxygenase, arachidonate 12-lipoxygenase, leukocyte-type, arachidonate omega-6 lipoxygenase
- Nigam S, Zafiriou M. Hepoxilin A3 synthase. Biochem Biophys Res Commun. 2005;338:161-8 pubmed
- Liu Y, Tang X, Lu C, Han W, Guo S, Zhu D. Expression of 15-lipoxygenases in pulmonary arteries after hypoxia. Pathology. 2009;41:476-83 pubmed..Moreover, the expressions of both 15-LOX isoenzymes increased dramatically after hypoxia. These results suggest that both isoenzymes of 15-LOXs are upregulated after hypoxia. ..
- Andersson E, Schain F, Svedling M, Claesson H, Forsell P. Interaction of human 15-lipoxygenase-1 with phosphatidylinositol bisphosphates results in increased enzyme activity. Biochim Biophys Acta. 2006;1761:1498-505 pubmed..Taken together, this report demonstrates that human 15-LO-1 binds to PI(4.5)P(2) and PI(3.4)P(2) and that these phospholipids stimulate enzyme activity in the presence of calcium in a vesicle based assay. ..
- Rostkowska Nadolska B, Kapral M, Fraczek M, Kowalczyk M, Gawron W, Mazurek U. A microarray study of gene expression profiles in nasal polyps. Auris Nasus Larynx. 2011;38:58-64 pubmed publisher..In the control group, significantly higher expression of DMBT1, ALOX12 and LTF genes was detected...
- Mabalirajan U, Aich J, Leishangthem G, Sharma S, Dinda A, Ghosh B. Effects of vitamin E on mitochondrial dysfunction and asthma features in an experimental allergic murine model. J Appl Physiol (1985). 2009;107:1285-92 pubmed publisher..In summary, these findings show that Vit-E reduces key mitochondrial dysfunctions and alleviates asthmatic features. ..
- Sun L, Xu Y, Han J, Liang H, Wang N, Cheng Y. 12/15-Lipoxygenase metabolites of arachidonic acid activate PPARÎ³: a possible neuroprotective effect in ischemic brain. J Lipid Res. 2015;56:502-14 pubmed publisher..Thus, the induction of 12(S)- and 15(S)-HETE during brain ischemia suggests that endogenous signals of neuroprotection may be generated. ..
- Zuo L, Christofi F, Wright V, Bao S, Clanton T. Lipoxygenase-dependent superoxide release in skeletal muscle. J Appl Physiol (1985). 2004;97:661-8 pubmed..These data show for the first time that arachidonic acid metabolism through LOX activity, is a major source of extracellular O(2)(*-) release in skeletal muscle. ..
- Nagasawa K, Kakuda T, Higashi Y, Fujimoto S. Possible involvement of 12-lipoxygenase activation in glucose-deprivation/reload-treated neurons. Neurosci Lett. 2007;429:120-5 pubmed..These findings suggested that activation of 12-LOX, but not NADPH oxidase, following to zinc release might play an important role in ROS generation and decrease of viability in GD/R-treated neurons. ..
- Gregus A, Dumlao D, Wei S, Norris P, Catella L, Meyerstein F, et al. Systematic analysis of rat 12/15-lipoxygenase enzymes reveals critical role for spinal eLOX3 hepoxilin synthase activity in inflammatory hyperalgesia. FASEB J. 2013;27:1939-49 pubmed publisher..We detected the following primary intrinsic activities: 12-LOX (Alox12, Alox15), 15-LOX (Alox15b), and HXS (Alox12, Alox15)...
- Zarbock A, Distasi M, Smith E, Sanders J, Kronke G, Harry B, et al. Improved survival and reduced vascular permeability by eliminating or blocking 12/15-lipoxygenase in mouse models of acute lung injury (ALI). J Immunol. 2009;183:4715-22 pubmed publisher..The vascular permeability increase upon LPS inhalation was abolished in Alox15(-/-) mice lacking 12/15-LO and in wild-type mice after pharmacological blockade of 12/15-LO...
- Uderhardt S, Herrmann M, Oskolkova O, Aschermann S, Bicker W, Ipseiz N, et al. 12/15-lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance. Immunity. 2012;36:834-46 pubmed publisher..Our data reveal an unexpected key role for enzymatic lipid oxidation during the maintenance of self-tolerance. ..
- Klein R, Allard J, Avnur Z, Nikolcheva T, Rotstein D, Carlos A, et al. Regulation of bone mass in mice by the lipoxygenase gene Alox15. Science. 2004;303:229-32 pubmed..Through combined genetic and genomic approaches, we identified the lipoxygenase gene Alox15 as a negative regulator of peak bone mineral density in mice...
- Xu Z, Li S, Lanting L, Kim Y, Shanmugam N, Reddy M, et al. Relationship between 12/15-lipoxygenase and COX-2 in mesangial cells: potential role in diabetic nephropathy. Kidney Int. 2006;69:512-9 pubmed..These new results indicate for the first time that 12/15-LO and COX-2 pathways can cross-talk and activate each other in MC. These novel interactions may amplify their effects on the progression of DN. ..
- Pidgeon G, Tang K, Rice R, Zacharek A, Li L, Taylor J, et al. Overexpression of leukocyte-type 12-lipoxygenase promotes W256 tumor cell survival by enhancing alphavbeta5 expression. Int J Cancer. 2003;105:459-71 pubmed..These results show that the 12-LOX pathway is a regulator of cell survival and apoptosis, by affecting the expression and localization of the alphavbeta5 integrin and actin microfilaments in Walker 256 cells...
- Weibel G, Joshi M, Wei C, Bates S, Blair I, Rothblat G. 15(S)-Lipoxygenase-1 associates with neutral lipid droplets in macrophage foam cells: evidence of lipid droplet metabolism. J Lipid Res. 2009;50:2371-6 pubmed publisher..We propose that 15-LO-1 is present and functional on cytoplasmic neutral lipid droplets in macrophage foam cells, and these droplets may act to accumulate the anti-inflammatory lipid mediator 15(S)-HETE. ..
- Katoh T, Lakkis F, Makita N, Badr K. Co-regulated expression of glomerular 12/15-lipoxygenase and interleukin-4 mRNAs in rat nephrotoxic nephritis. Kidney Int. 1994;46:341-9 pubmed..This represents the first demonstration of tandem regulated in vivo gene expression for a lymphokine (IL-4) and a lipoxygenase, both of which promote counter-inflammatory influences in immune complex-mediated injury. ..
- Prasad V, Nithipatikom K, Harder D. Ceramide elevates 12-hydroxyeicosatetraenoic acid levels and upregulates 12-lipoxygenase in rat primary hippocampal cell cultures containing predominantly astrocytes. Neurochem Int. 2008;53:220-9 pubmed publisher..Induction of 12-LOX pathway by ceramide may have implications in understanding pathophysiology of neurodegenerative diseases involving ROS generation and inflammation. ..
- Sloane D, Leung R, Craik C, Sigal E. A primary determinant for lipoxygenase positional specificity. Nature. 1991;354:149-52 pubmed..Other mutations at the neighbouring amino acids 416 and 417 give an enzyme which performs 12- and 15-lipoxygenation in a ratio of 15:1. These results indicate that this region might position the substrate in the active site. ..
- Preston I, Hill N, Warburton R, Fanburg B. Role of 12-lipoxygenase in hypoxia-induced rat pulmonary artery smooth muscle cell proliferation. Am J Physiol Lung Cell Mol Physiol. 2006;290:L367-74 pubmed..We conclude that 12-LO and its product, 12(S)-HETE, are important intermediates in hypoxia-induced pulmonary artery SMC proliferation and may participate in hypoxia-induced pulmonary hypertension. ..
- Li J, Rao J, Liu Y, Cao Y, Zhang Y, Zhang Q, et al. 15-Lipoxygenase promotes chronic hypoxia-induced pulmonary artery inflammation via positive interaction with nuclear factor-?B. Arterioscler Thromb Vasc Biol. 2013;33:971-9 pubmed publisher..Our study revealed a novel mechanism underlying hypoxia-induced pulmonary arterial inflammation and suggested new therapeutic strategies targeting 15-LO/15-HETE and nuclear factor-?B in the treatment of pulmonary arterial hypertension. ..
- Tanabe M, Kamitani H, Watanabe T, Radmark O. C-terminus of p47(phox) is required for interaction with leukocyte type rat 12-lipoxygenase. Protein Pept Lett. 2005;12:295-7 pubmed..These results indicate that C-terminus of p47(phox) is important for its interaction to rat 12-LO. ..
- Sun D, Funk C. Disruption of 12/15-lipoxygenase expression in peritoneal macrophages. Enhanced utilization of the 5-lipoxygenase pathway and diminished oxidation of low density lipoprotein. J Biol Chem. 1996;271:24055-62 pubmed..Thus, 12/15-lipoxygenase-deficient mice will be useful for the study of interaction between lipoxygenase pathways and determination of the in vivo role of 12/15-lipoxygenase-catalyzed oxidation of LDL in atherogenesis. ..
- Coffey M, Natarajan R, Chumley P, Coles B, Thimmalapura P, Nowell M, et al. Catalytic consumption of nitric oxide by 12/15- lipoxygenase: inhibition of monocyte soluble guanylate cyclase activation. Proc Natl Acad Sci U S A. 2001;98:8006-11 pubmed
- Emerson M, Levine S. Experimental allergic encephalomyelitis is exacerbated in mice deficient for 12/15-lipoxygenase or 5-lipoxygenase. Brain Res. 2004;1021:140-5 pubmed..Continued analysis will provide insight into the endogenous LO-generated effectors that assist in tempering EAE. ..
- Nigam S, Patabhiraman S, Ciccoli R, Ishdorj G, Schwarz K, Petrucev B, et al. The rat leukocyte-type 12-lipoxygenase exhibits an intrinsic hepoxilin A3 synthase activity. J Biol Chem. 2004;279:29023-30 pubmed..In summary, it may be concluded that naturally occurring 12S-lipoxygenases exhibit an intrinsic hepoxilin A(3) synthase activity that is minimal in lipoxygenase isoforms with different positional specificity. ..
- Singh N, Wang D, Kundumani Sridharan V, Van Quyen D, Niu J, Rao G. 15-Lipoxygenase-1-enhanced Src-Janus kinase 2-signal transducer and activator of transcription 3 stimulation and monocyte chemoattractant protein-1 expression require redox-sensitive activation of epidermal growth factor receptor in vascular wall rem. J Biol Chem. 2011;286:22478-88 pubmed publisher
- Obrosova I, Stavniichuk R, Drel V, Shevalye H, Vareniuk I, Nadler J, et al. Different roles of 12/15-lipoxygenase in diabetic large and small fiber peripheral and autonomic neuropathies. Am J Pathol. 2010;177:1436-47 pubmed publisher..This should be considered in the selection of endpoints for future clinical trials of 12/15-lipoxygenase inhibitors. ..
- Yang H, Zhuo J, Chu J, Chinnici C, Pratico D. Amelioration of the Alzheimer's disease phenotype by absence of 12/15-lipoxygenase. Biol Psychiatry. 2010;68:922-9 pubmed publisher..Our findings support the novel hypothesis that blockade of 12/15LO in the central nervous system by modulating BACE proteolytic pathway could be an effective therapy for prevention or treatment of AD. ..
- Wakabayashi M, Yoshioka T, Higashino K, Numata Y, Igarashi Y, Kihara A. Decreases in 15-lipoxygenase metabolites in Olmsted syndrome model rats. J Dermatol Sci. 2017;85:186-196 pubmed publisher..Consistent with the decreases in the 15-LOX metabolites, expression levels of the genes that encode the 15-LOXs, Alox15 and Alox15b, were largely reduced...
- Reddy M, Sahar S, Villeneuve L, Lanting L, Natarajan R. Role of Src tyrosine kinase in the atherogenic effects of the 12/15-lipoxygenase pathway in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 2009;29:387-93 pubmed publisher..Src kinase signaling plays a central role in the proatherogenic responses mediated by 12/15-LO and its oxidized lipid metabolite 12(S)-HETE in VSMCs. ..
- Zhao J, O Donnell V, Balzar S, St Croix C, Trudeau J, Wenzel S. 15-Lipoxygenase 1 interacts with phosphatidylethanolamine-binding protein to regulate MAPK signaling in human airway epithelial cells. Proc Natl Acad Sci U S A. 2011;108:14246-51 pubmed publisher..The results confirm a previously unknown signaling role for 15LO1 and its PE-conjugated eicosanoid product in human airway epithelial cells. This pathway enhances critical inflammatory pathways integral to asthma pathogenesis. ..
- SEARS D, Miles P, Chapman J, Ofrecio J, Almazan F, Thapar D, et al. 12/15-lipoxygenase is required for the early onset of high fat diet-induced adipose tissue inflammation and insulin resistance in mice. PLoS ONE. 2009;4:e7250 pubmed publisher..These results demonstrate that 12/15LO mediates early stages of adipose tissue inflammation and whole body insulin resistance induced by high fat feeding. ..
- Hajek A, Lindley A, Favoreto S, Carter R, Schleimer R, Kuperman D. 12/15-Lipoxygenase deficiency protects mice from allergic airways inflammation and increases secretory IgA levels. J Allergy Clin Immunol. 2008;122:633-9.e3 pubmed publisher..Induction of 15-LO-1 in asthma might contribute to allergic sensitization and airways inflammation, potentially by causing suppression of secretory IgA. ..
- Coffey R, Nam H, Knutson M. Microarray analysis of rat pancreas reveals altered expression of Alox15 and regenerating islet-derived genes in response to iron deficiency and overload. PLoS ONE. 2014;9:e86019 pubmed publisher..The most up-regulated transcript in iron-deficient pancreas was arachidonate 15-lipoxygenase (Alox15), which has been implicated in the development of diabetes...
- Biteman B, Hassan I, Walker E, Leedom A, Dunn M, Seta F, et al. Interdependence of lipoxin A4 and heme-oxygenase in counter-regulating inflammation during corneal wound healing. FASEB J. 2007;21:2257-66 pubmed..Collectively, results demonstrate a critical role for LXA4 in inflammatory/reparative responses and provide the first evidence that 12/15-LOX and HO systems function in concert to control inflammation. ..
- Kayama Y, Minamino T, Toko H, Sakamoto M, Shimizu I, Takahashi H, et al. Cardiac 12/15 lipoxygenase-induced inflammation is involved in heart failure. J Exp Med. 2009;206:1565-74 pubmed publisher..Among the genes analyzed, Alox15 encoding the protein 12/15 lipoxygenase (LOX) was markedly up-regulated in heart failure...
- Huang J, Welch J, Ricote M, Binder C, Willson T, Kelly C, et al. Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase. Nature. 1999;400:378-82 pubmed..These findings reveal a physiological role of 12/15-lipoxygenase in the generation of endogenous ligands for PPAR-gamma, and suggest a paradigm for the regulation of nuclear receptor function by cytokines. ..
- Viita H, Pacholska A, Ahmad F, Tietäväinen J, Naarala J, Hyvärinen A, et al. 15-Lipoxygenase-1 induces lipid peroxidation and apoptosis, and improves survival in rat malignant glioma. In Vivo. 2012;26:1-8 pubmed..001). Our results support the pro-apoptotic role of 15-lipoxygenase-1 and suggest that 15-lipoxygenase-1 could be a potential new target gene for the therapy of malignant glioma. ..
- Cui L, Zhang X, Yang R, Wang L, Liu L, Li M, et al. Neuroprotection of early and short-time applying atorvastatin in the acute phase of cerebral ischemia: down-regulated 12/15-LOX, p38MAPK and cPLA2 expression, ameliorated BBB permeability. Brain Res. 2010;1325:164-73 pubmed publisher..Atorvastatin protected brain from damage caused by MCAO at the early stage; this effect may be through down-regulation of 12/15-LOX, p38MAPK and cPLA2 expressions, and ameliorating BBB permeability. ..
- Alonso Galicia M, Maier K, Greene A, Cowley A, Roman R. Role of 20-hydroxyeicosatetraenoic acid in the renal and vasoconstrictor actions of angiotensin II. Am J Physiol Regul Integr Comp Physiol. 2002;283:R60-8 pubmed
- Li Q, Mao M, Qiu Y, Liu G, Sheng T, Yu X, et al. Key Role of ROS in the Process of 15-Lipoxygenase/15-Hydroxyeicosatetraenoiccid-Induced Pulmonary Vascular Remodeling in Hypoxia Pulmonary Hypertension. PLoS ONE. 2016;11:e0149164 pubmed publisher..These results indicated that 15-HETE-regulated ROS mediated hypoxia-induced pulmonary vascular remodeling (PVR) via the p38 MAPK pathway. ..
- Chang W, Nakao J, Orimo H, Murota S. Effects of reduced glutathione on the 12-lipoxygenase pathways in rat platelets. Biochem J. 1982;202:771-6 pubmed..Fractionation of cell homogenates indicates that the cytosol fraction possesses almost all the 12-lipoxygenase activity, whereas the microsomal fraction exhibits little enzyme activity. ..
- Cole B, Kuhn N, Green Mitchell S, Leone K, Raab R, Nadler J, et al. 12/15-Lipoxygenase signaling in the endoplasmic reticulum stress response. Am J Physiol Endocrinol Metab. 2012;302:E654-65 pubmed publisher..Therefore, reduction of 12/15-LO activity or expression could provide a new therapeutic target to reduce ER stress and downstream inflammation linked to obesity...
- Tang L, Ding T, Pratico D. Additive anti-atherogenic effect of thromboxane receptor antagonism with 12/15lipoxygenase gene disruption in apolipoprotein E-deficient mice. Atherosclerosis. 2008;199:265-70 pubmed publisher..These results suggest that the 12/15LO- and TxA(2) receptor-mediated pro-atherogenic effects are two distinct pathways and represent two separate therapeutic targets for a better anti-atherogenic strategy. ..
- Kuwata H, Nonaka T, Murakami M, Kudo I. Search of factors that intermediate cytokine-induced group IIA phospholipase A2 expression through the cytosolic phospholipase A2- and 12/15-lipoxygenase-dependent pathway. J Biol Chem. 2005;280:25830-9 pubmed
- Gronert K, Maheshwari N, Khan N, Hassan I, Dunn M, Laniado Schwartzman M. A role for the mouse 12/15-lipoxygenase pathway in promoting epithelial wound healing and host defense. J Biol Chem. 2005;280:15267-78 pubmed..Here, we demonstrate that mouse corneas generate endogenous LXA(4) and NPD1. 12/15-LOX (Alox15) and LXA(4) receptor mRNA expression as well as LXA(4) formation were abrogated by epithelial removal and restored ..
- Miller Y, Chang M, Funk C, Feramisco J, Witztum J. 12/15-lipoxygenase translocation enhances site-specific actin polymerization in macrophages phagocytosing apoptotic cells. J Biol Chem. 2001;276:19431-9 pubmed..These studies suggest that the 12/15-LO enzyme plays a major role in local control of actin polymerization in macrophages in response to interaction with apoptotic cells. ..
- Kronke G, Katzenbeisser J, Uderhardt S, Zaiss M, Scholtysek C, Schabbauer G, et al. 12/15-lipoxygenase counteracts inflammation and tissue damage in arthritis. J Immunol. 2009;183:3383-9 pubmed publisher..Taken together, these results support an anti-inflammatory and tissue-protective role of 12/15-LO and its products during chronic inflammatory disorders such as arthritis. ..
- Hada T, Hagiya H, Suzuki H, Arakawa T, Nakamura M, Matsuda S, et al. Arachidonate 12-lipoxygenase of rat pineal glands: catalytic properties and primary structure deduced from its cDNA. Biochim Biophys Acta. 1994;1211:221-8 pubmed..The predominant presence of 12-lipoxygenase mRNA in pineal gland was confirmed by in situ hybridization of rat brain. Significant amounts of 12-lipoxygenase mRNA were also detected in rat spleen, aorta, lung and leukocytes. ..
- Dioszeghy V, Rosas M, Maskrey B, Colmont C, Topley N, Chaitidis P, et al. 12/15-Lipoxygenase regulates the inflammatory response to bacterial products in vivo. J Immunol. 2008;181:6514-24 pubmed..No changes in neutrophil or lymphocyte numbers were seen. In summary, endogenous 12/15-LOX defines the resident MPhi population and regulates both the recruitment of monocytes/Mphi and cytokine response to bacterial products in vivo. ..
- Zheng H, Stratton C, Morozumi K, Jin J, Yanagimachi R, Yan W. Lack of Spem1 causes aberrant cytoplasm removal, sperm deformation, and male infertility. Proc Natl Acad Sci U S A. 2007;104:6852-7 pubmed..Our study reveals that proper cytoplasm removal is a genetically regulated process requiring the participation of Spem1 and that lack of Spem1 causes sperm deformation and male infertility. ..
- Andersson K, Florholmen G, Winer L, Tønnessen T, Christensen G. Regulation of neuronal type genes in congestive heart failure rats. Acta Physiol (Oxf). 2006;186:17-27 pubmed..1 (Ddr1), neuronal pentraxin receptor (Nptxr), peripheral myelin protein Pmp-22, leukocyte type 12-lipoxygenase (Alox15), cytochrome P450 4F5 (Cyp4F5) and cardiac Kcne1 were all increased (range 1.6-6.0-fold, P < 0...
- Pratico D, Zhukareva V, Yao Y, Uryu K, Funk C, Lawson J, et al. 12/15-lipoxygenase is increased in Alzheimer's disease: possible involvement in brain oxidative stress. Am J Pathol. 2004;164:1655-62 pubmed..These data show that the 12/15-LOX metabolic pathway is increased and correlates with an oxidative imbalance in the AD brain, implying that this enzyme might contribute to the pathogenesis of this neurodegenerative disorder. ..