Alox15

Summary

Gene Symbol: Alox15
Description: arachidonate 15-lipoxygenase
Alias: 12-LO, 12/15-LO, 15-LOX, Alox12l, L-12LO, arachidonate 15-lipoxygenase, 12-LOX, 12/15-lipoxygenase, arachidonate 12-lipoxygenase, leukocyte-type, arachidonate omega-6 lipoxygenase
Species: mouse
Products:     Alox15

Top Publications

  1. 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. ..
  2. McDuffie M, Maybee N, Keller S, Stevens B, Garmey J, Morris M, et al. Nonobese diabetic (NOD) mice congenic for a targeted deletion of 12/15-lipoxygenase are protected from autoimmune diabetes. Diabetes. 2008;57:199-208 pubmed
    ..Since the gene encoding 12/15-LO (gene designation Alox15) lies within the Idd4 diabetes susceptibility interval in NOD mice, we hypothesized that 12/15-LO is also a key ..
  3. Dwarakanath R, Sahar S, Lanting L, Wang N, Stemerman M, Natarajan R, et al. Viral vector-mediated 12/15-lipoxygenase overexpression in vascular smooth muscle cells enhances inflammatory gene expression and migration. J Vasc Res. 2008;45:132-42 pubmed
    ..Enhanced proatherogenic responses in VSMCs triggered by increased 12/15-LO levels under pathological conditions may contribute to vascular dysfunction. ..
  4. George J, Afek A, Shaish A, Levkovitz H, Bloom N, Cyrus T, et al. 12/15-Lipoxygenase gene disruption attenuates atherogenesis in LDL receptor-deficient mice. Circulation. 2001;104:1646-50 pubmed
    ..12/15-LO plays a dominant role in promoting atherogenesis in LDL-R(-/-) mice. ..
  5. Bleich D, Chen S, Zipser B, Sun D, Funk C, Nadler J. Resistance to type 1 diabetes induction in 12-lipoxygenase knockout mice. J Clin Invest. 1999;103:1431-6 pubmed
    ..In summary, elimination of leukocyte 12-LO in mice ameliorates low dose streptozotocin-induced diabetes by increasing islet resistance to cytokines and decreasing macrophage production of nitric oxide. ..
  6. Cyrus T, Witztum J, Rader D, Tangirala R, Fazio S, Linton M, et al. Disruption of the 12/15-lipoxygenase gene diminishes atherosclerosis in apo E-deficient mice. J Clin Invest. 1999;103:1597-604 pubmed
    ..The combined data indicate a role for 12/15-lipoxygenase in the pathogenesis of atherosclerosis and suggest that inhibition of this enzyme may decrease disease progression. ..
  7. van Leyen K, Kim H, Lee S, Jin G, Arai K, Lo E. Baicalein and 12/15-lipoxygenase in the ischemic brain. Stroke. 2006;37:3014-8 pubmed
    ..In contrast, the 12/15-LOX knockout mice are not further protected by baicalein. Baicalein protects against ischemia/reperfusion injury by inhibiting the 12/15-lipoxygenase pathway to neuronal cell death. ..
  8. Chakrabarti S, Cole B, Wen Y, Keller S, Nadler J. 12/15-lipoxygenase products induce inflammation and impair insulin signaling in 3T3-L1 adipocytes. Obesity (Silver Spring). 2009;17:1657-63 pubmed publisher
  9. 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 ..

More Information

Publications83

  1. Huo Y, Zhao L, Hyman M, Shashkin P, Harry B, Burcin T, et al. Critical role of macrophage 12/15-lipoxygenase for atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2004;110:2024-31 pubmed
    ..We conclude that macrophage 12/15-LO plays a dominant role in the development of atherosclerosis by promoting endothelial inflammation and foam cell formation. ..
  2. Martínez Clemente M, Ferre N, Titos E, Horrillo R, González Périz A, Morán Salvador E, et al. Disruption of the 12/15-lipoxygenase gene (Alox15) protects hyperlipidemic mice from nonalcoholic fatty liver disease. Hepatology. 2010;52:1980-91 pubmed publisher
    We have shown that Alox15, the gene encoding for 12/15-lipoxygenase (12/15-LO), is markedly up-regulated in livers from apolipoprotein E-deficient (ApoE(-/-)) mice, which spontaneously develop nonalcoholic fatty liver disease secondary to ..
  3. Zhao L, Cuff C, Moss E, Wille U, Cyrus T, Klein E, et al. Selective interleukin-12 synthesis defect in 12/15-lipoxygenase-deficient macrophages associated with reduced atherosclerosis in a mouse model of familial hypercholesterolemia. J Biol Chem. 2002;277:35350-6 pubmed
    ..The data provide support for a novel mechanism linking the 12/15-lipoxygenase pathway to a known immunomodulatory Th1 cytokine in atherogenesis. ..
  4. Funk C. The molecular biology of mammalian lipoxygenases and the quest for eicosanoid functions using lipoxygenase-deficient mice. Biochim Biophys Acta. 1996;1304:65-84 pubmed
  5. 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. ..
  6. Li S, Dwarakanath R, Cai Q, Lanting L, Natarajan R. Effects of silencing leukocyte-type 12/15-lipoxygenase using short interfering RNAs. J Lipid Res. 2005;46:220-9 pubmed
    ..Our results illustrate the functional relevance of 12/15-LO activation in macrophages and VSMCs and its relationship to oxidant stress and inflammation. ..
  7. Al Shabrawey M, Mussell R, Kahook K, Tawfik A, Eladl M, Sarthy V, et al. Increased expression and activity of 12-lipoxygenase in oxygen-induced ischemic retinopathy and proliferative diabetic retinopathy: implications in retinal neovascularization. Diabetes. 2011;60:614-24 pubmed publisher
    ..The goal of this study was to investigate whether 12-LOX plays a role in retinal neovascularization (NV)...
  8. 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. ..
  9. Jeon S, Moon H, Kim Y, Choi J, Shin T, Hong S, et al. 15-lipoxygenase metabolites play an important role in the development of a T-helper type 1 allergic inflammation induced by double-stranded RNA. Clin Exp Allergy. 2009;39:908-17 pubmed publisher
    ..Our findings suggest that the 15-LO pathway is a novel therapeutic target for the treatment of virus-associated asthma characterized by Th1 inflammation. ..
  10. Gubitosi Klug R, Talahalli R, Du Y, Nadler J, Kern T. 5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of retinal capillaries in a mouse model of diabetic retinopathy. Diabetes. 2008;57:1387-93 pubmed publisher
    ..5-Lipoxygenase represents a novel pathway for therapeutic intervention of diabetic retinopathy. ..
  11. Paintlia A, Paintlia M, Singh I, Singh A. IL-4-induced peroxisome proliferator-activated receptor gamma activation inhibits NF-kappaB trans activation in central nervous system (CNS) glial cells and protects oligodendrocyte progenitors under neuroinflammatory disease conditions: implication . J Immunol. 2006;176:4385-98 pubmed
  12. Jin G, Arai K, Murata Y, Wang S, Stins M, Lo E, et al. Protecting against cerebrovascular injury: contributions of 12/15-lipoxygenase to edema formation after transient focal ischemia. Stroke. 2008;39:2538-43 pubmed publisher
    ..12/15-LOX inhibitors may thus be effective as both neuroprotectants and vasculoprotectants. ..
  13. Andersson C, Claesson H, Rydell Törmänen K, Swedmark S, Hällgren A, Erjefalt J. Mice lacking 12/15-lipoxygenase have attenuated airway allergic inflammation and remodeling. Am J Respir Cell Mol Biol. 2008;39:648-56 pubmed publisher
    ..Hence, pharmacologic targeting of the human 15-LO-1 may represent an attractive therapeutic strategy to control inflammation and remodeling in asthma. ..
  14. 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...
  15. Chen X, Kurre U, Jenkins N, Copeland N, Funk C. cDNA cloning, expression, mutagenesis of C-terminal isoleucine, genomic structure, and chromosomal localizations of murine 12-lipoxygenases. J Biol Chem. 1994;269:13979-87 pubmed
    ..Antibodies prepared against the two forms of 12-lipoxygenase revealed the differential distribution of the two enzymes throughout the mouse. ..
  16. 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. ..
  17. 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. ..
  18. 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...
  19. 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. ..
  20. Cyrus T, Pratico D, Zhao L, Witztum J, Rader D, Rokach J, et al. Absence of 12/15-lipoxygenase expression decreases lipid peroxidation and atherogenesis in apolipoprotein e-deficient mice. Circulation. 2001;103:2277-82 pubmed
    ..Strong positive correlations exist between lesion size, isoprostane levels, and MDA-LDL autoantibodies, providing in vivo evidence for an enzymatic (12/15-LO) component to lipid peroxidation and atherogenesis. ..
  21. 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...
  22. Bolick D, Srinivasan S, Whetzel A, Fuller L, Hedrick C. 12/15 lipoxygenase mediates monocyte adhesion to aortic endothelium in apolipoprotein E-deficient mice through activation of RhoA and NF-kappaB. Arterioscler Thromb Vasc Biol. 2006;26:1260-6 pubmed
    ..Induction of ICAM-1 on aortic endothelium stimulates monocyte:endothelial adhesion in vivo in apoEKO mice. ..
  23. Wen Y, Gu J, Chakrabarti S, Aylor K, Marshall J, Takahashi Y, et al. The role of 12/15-lipoxygenase in the expression of interleukin-6 and tumor necrosis factor-alpha in macrophages. Endocrinology. 2007;148:1313-22 pubmed
    ..These results suggest a potentially important mechanism linking 12/15-LO activation to chronic inflammation and atherosclerosis. ..
  24. Middleton M, Rubinstein T, Pure E. Cellular and molecular mechanisms of the selective regulation of IL-12 production by 12/15-lipoxygenase. J Immunol. 2006;176:265-74 pubmed
    ..LPS-stimulated elicited peritoneal macrophages derived from 12/15-LO-deficient (Alox15) mice produced reduced IL-12 and IL-23 levels, but comparable amounts of several other inflammatory mediators ..
  25. Wen Y, Gu J, Vandenhoff G, Liu X, Nadler J. Role of 12/15-lipoxygenase in the expression of MCP-1 in mouse macrophages. Am J Physiol Heart Circ Physiol. 2008;294:H1933-8 pubmed publisher
    ..These results suggest a potentially important mechanism linking 12/15-LO activation to MCP-1 expression that induces inflammatory cell infiltration. ..
  26. Isobe Y, Arita M, Matsueda S, Iwamoto R, Fujihara T, Nakanishi H, et al. Identification and structure determination of novel anti-inflammatory mediator resolvin E3, 17,18-dihydroxyeicosapentaenoic acid. J Biol Chem. 2012;287:10525-34 pubmed publisher
    ..Both 18R- and 18S-RvE3 inhibited neutrophil chemotaxis in vitro at low nanomolar concentrations. These findings suggest that RvE3 contributes to the beneficial actions of EPA in controlling inflammation and related diseases. ..
  27. 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. ..
  28. Seiler A, Schneider M, Forster H, Roth S, Wirth E, Culmsee C, et al. Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab. 2008;8:237-48 pubmed publisher
    ..Since oxidative stress is common in the etiology of many human disorders, the identified pathway reveals promising targets for future therapies. ..
  29. Nunemaker C, Chen M, Pei H, Kimble S, Keller S, Carter J, et al. 12-Lipoxygenase-knockout mice are resistant to inflammatory effects of obesity induced by Western diet. Am J Physiol Endocrinol Metab. 2008;295:E1065-75 pubmed publisher
    ..Inhibiting 12-LO may provide a new therapeutic approach to prevent inflammation-mediated metabolic consequences of excess fat intake. ..
  30. Mao F, Xu M, Zuo X, Yu J, Xu W, Moussalli M, et al. 15-Lipoxygenase-1 suppression of colitis-associated colon cancer through inhibition of the IL-6/STAT3 signaling pathway. FASEB J. 2015;29:2359-70 pubmed publisher
    ..25 in 15-LOX-1-PPAR-δ-Gut mice (P = 0.0006). Identification of 15-LOX-1 suppression of PPAR-δ to inhibit IL-6/STAT3 signaling-driven CAC tumorigenesis provides mechanistic insights that can be used to molecularly target CAC. ..
  31. Claesson H. On the biosynthesis and biological role of eoxins and 15-lipoxygenase-1 in airway inflammation and Hodgkin lymphoma. Prostaglandins Other Lipid Mediat. 2009;89:120-5 pubmed publisher
    ..The putative therapeutic implications of 15-LO-1 inhibitors in the treatment of asthma, chronic obstructive pulmonary disorder and Hodgkin lymphoma are discussed...
  32. 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. ..
  33. Lindley A, Crapster Pregont M, Liu Y, Kuperman D. 12/15-lipoxygenase is an interleukin-13 and interferon-? counterregulated-mediator of allergic airway inflammation. Mediators Inflamm. 2010;2010: pubmed publisher
    ..Interleukin-13 and interferon-? counterregulate 12/15-lipoxygenase potentially contributing to the effects of these cytokines on allergic airway inflammation. ..
  34. Pallast S, Arai K, Pekcec A, Yigitkanli K, Yu Z, Wang X, et al. Increased nuclear apoptosis-inducing factor after transient focal ischemia: a 12/15-lipoxygenase-dependent organelle damage pathway. J Cereb Blood Flow Metab. 2010;30:1157-67 pubmed publisher
    ..0%+/-2.7%), suggesting cell death through organelle damage. Taken together, these findings show that 12/15-LOX and AIF are sequential actors in a common cell death pathway that may contribute to stroke-induced brain damage. ..
  35. Krieg P, Rosenberger S, de Juanes S, Latzko S, Hou J, Dick A, et al. Aloxe3 knockout mice reveal a function of epidermal lipoxygenase-3 as hepoxilin synthase and its pivotal role in barrier formation. J Invest Dermatol. 2013;133:172-80 pubmed publisher
  36. Zuo X, Peng Z, Wu Y, Moussalli M, Yang X, Wang Y, et al. Effects of gut-targeted 15-LOX-1 transgene expression on colonic tumorigenesis in mice. J Natl Cancer Inst. 2012;104:709-16 pubmed publisher
  37. Kriska T, Cepura C, Magier D, Siangjong L, Gauthier K, Campbell W. Mice lacking macrophage 12/15-lipoxygenase are resistant to experimental hypertension. Am J Physiol Heart Circ Physiol. 2012;302:H2428-38 pubmed publisher
    In mouse arteries, Alox15 [leukocyte-type 12/15-lipoxygenase (LO)] is assumed to regulate vascular function by metabolizing arachidonic acid (AA) to dilator eicosanoids that mediate the endothelium-dependent relaxations to AA and ..
  38. Krieg P, Kinzig A, Heidt M, Marks F, Furstenberger G. cDNA cloning of a 8-lipoxygenase and a novel epidermis-type lipoxygenase from phorbol ester-treated mouse skin. Biochim Biophys Acta. 1998;1391:7-12 pubmed
    ..Based on these data, we conclude that this epidermis-derived cDNA encodes a novel lipoxygenase isoform termed provisionally epidermis-type lipoxygenase 2 (e-LOX 2). ..
  39. Yigitkanli K, Zheng Y, Pekcec A, Lo E, van Leyen K. Increased 12/15-Lipoxygenase Leads to Widespread Brain Injury Following Global Cerebral Ischemia. Transl Stroke Res. 2017;8:194-202 pubmed publisher
  40. Stein K, Stoffels M, Lysson M, Schneiker B, Dewald O, Krönke G, et al. A role for 12/15-lipoxygenase-derived proresolving mediators in postoperative ileus: protectin DX-regulated neutrophil extravasation. J Leukoc Biol. 2016;99:231-9 pubmed publisher
    ..Perioperative, parenteral protectin DX or docosahexaenoic acid supplementation, as well as modulation of the 12/15-lipoxygenase pathway, may be instrumental in prevention of postoperative ileus. ..
  41. Zhao L, Pratico D, Rader D, Funk C. 12/15-Lipoxygenase gene disruption and vitamin E administration diminish atherosclerosis and oxidative stress in apolipoprotein E deficient mice through a final common pathway. Prostaglandins Other Lipid Mediat. 2005;78:185-93 pubmed
    ..These results suggest that early 12/15-LO-mediated lipid peroxidation triggers ensuing non-enzymatic peroxidation that is susceptible to Vitamin E antioxidant action in a common pathway of atherogenesis. ..
  42. Brütsch S, Rademacher M, Roth S, Muller K, Eder S, Viertel D, et al. Male Subfertility Induced by Heterozygous Expression of Catalytically Inactive Glutathione Peroxidase 4 Is Rescued in Vivo by Systemic Inactivation of the Alox15 Gene. J Biol Chem. 2016;291:23578-23588 pubmed
    Glutathione peroxidase 4 (GPX4) and arachidonic acid 15-lipoxygenase (ALOX15) are antagonizing enzymes in the metabolism of hydroperoxy lipids...
  43. TURMAN M, Kingsley P, Rouzer C, Cravatt B, Marnett L. Oxidative metabolism of a fatty acid amide hydrolase-regulated lipid, arachidonoyltaurine. Biochemistry. 2008;47:3917-25 pubmed publisher
    ..Over prolonged incubations, RPMs also generated small amounts of diHETE-T. Oxidative metabolism of polyunsaturated N-acyltaurines may represent a pathway for the generation or termination of novel signaling molecules. ..
  44. Yeung J, Tourdot B, Fernandez Perez P, Vesci J, Ren J, Smyrniotis C, et al. Platelet 12-LOX is essential for Fc?RIIa-mediated platelet activation. Blood. 2014;124:2271-9 pubmed publisher
    ..These results support an essential role for 12-LOX in regulating Fc?RIIa-mediated platelet function and identifies 12-LOX as a potential therapeutic target to limit immune-mediated thrombosis. ..
  45. Chen Y, Peng C, Abraham S, Shan Y, Guo Z, DeSouza N, et al. Arachidonate 15-lipoxygenase is required for chronic myeloid leukemia stem cell survival. J Clin Invest. 2014;124:3847-62 pubmed publisher
    ..Here, we determined that the gene encoding arachidonate 15-lipoxygenase (Alox15/15-LO) is essential for the survival of leukemia stem cells (LSCs) in a murine model of BCR-ABL-induced chronic ..
  46. Weaver J, Holman T, Imai Y, Jadhav A, Kenyon V, Maloney D, et al. Integration of pro-inflammatory cytokines, 12-lipoxygenase and NOX-1 in pancreatic islet beta cell dysfunction. Mol Cell Endocrinol. 2012;358:88-95 pubmed publisher
    ..Inhibitors of this pathway may provide a new therapeutic strategy to preserve beta cell mass in diabetes. ..
  47. Titterington J, Sukhanov S, Higashi Y, Vaughn C, BOWERS C, Delafontaine P. Growth hormone-releasing peptide-2 suppresses vascular oxidative stress in ApoE-/- mice but does not reduce atherosclerosis. Endocrinology. 2009;150:5478-87 pubmed publisher
    ..In summary, GHRP-2 exerts antioxidant effects in vivo and in vitro but does not reduce plaque burden. The lack of an antiatherogenic effect may be due to GH-dependent effects in vivo, thereby blunting the effect of increased IGF-I. ..
  48. Kriska T, Cepura C, Gauthier K, Campbell W. Role of macrophage PPAR? in experimental hypertension. Am J Physiol Heart Circ Physiol. 2014;306:H26-32 pubmed publisher
    Targeted disruption of the Alox15 gene makes mice resistant to angiotensin II-, DOCA/salt-, and N(?)-nitro-L-arginine methyl ester (L-NAME)-induced experimental hypertension...
  49. Merched A, Serhan C, Chan L. Nutrigenetic disruption of inflammation-resolution homeostasis and atherogenesis. J Nutrigenet Nutrigenomics. 2011;4:12-24 pubmed publisher
    ..These findings underscore the importance of dietary essential PUFAs and LOX-derived lipid mediators in combination with lipid-lowering agents in the prevention and treatment of atherosclerotic cardiovascular diseases. ..
  50. Tersey S, Maier B, Nishiki Y, Maganti A, Nadler J, Mirmira R. 12-lipoxygenase promotes obesity-induced oxidative stress in pancreatic islets. Mol Cell Biol. 2014;34:3735-45 pubmed publisher
    ..Our data reveal a novel pathway in which islet 12-LO suppresses antioxidant enzymes and prevents the adaptive islet responses in the setting of high-fat diets. ..
  51. Freire Moar J, Alavi Nassab A, Ng M, Mulkins M, Sigal E. Cloning and characterization of a murine macrophage lipoxygenase. Biochim Biophys Acta. 1995;1254:112-6 pubmed
    ..A partial genomic clone for this lipoxygenase has also been characterized. Southern blot analysis of mouse genomic DNA indicates that this is a single copy gene. ..
  52. Middleton M, Zukas A, Rubinstein T, Jacob M, Zhu P, Zhao L, et al. Identification of 12/15-lipoxygenase as a suppressor of myeloproliferative disease. J Exp Med. 2006;203:2529-40 pubmed
    ..Although not associated with dysregulation of Abl, cells isolated from chronic stage 12/15-LO-deficient (Alox15) mice exhibit increased activation of the phosphatidylinositol 3-kinase (PI3-K) pathway, as indicated by enhanced ..
  53. Rossaint J, Nadler J, Ley K, Zarbock A. Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury. Crit Care. 2012;16:R166 pubmed publisher
    ..The increase in neutrophil recruitment following LPS inhalation was reduced in 12/15-LO-deficient (Alox15(-/-)) mice and in wild-type (WT) mice after the blocking of 12/15-LO with a pharmacological inhibitor...
  54. Halade G, Kain V, Ingle K, Prabhu S. Interaction of 12/15-lipoxygenase with fatty acids alters the leukocyte kinetics leading to improved postmyocardial infarction healing. Am J Physiol Heart Circ Physiol. 2017;313:H89-H102 pubmed publisher
  55. Liu S, Xie Z, Zhao Q, Pang H, Turk J, Calderon L, et al. Smooth muscle-specific expression of calcium-independent phospholipase A2? (iPLA2?) participates in the initiation and early progression of vascular inflammation and neointima formation. J Biol Chem. 2012;287:24739-53 pubmed publisher
  56. Vahsen S, Rakowski K, Ledwig D, Dietze Schroeder D, Swifka J, Sasson S, et al. Altered GLUT4 translocation in skeletal muscle of 12/15-lipoxygenase knockout mice. Horm Metab Res. 2006;38:391-6 pubmed
  57. Park H, Khanna S, Rink C, Gnyawali S, Roy S, Sen C. Glutathione disulfide induces neural cell death via a 12-lipoxygenase pathway. Cell Death Differ. 2009;16:1167-79 pubmed publisher
    ..Strategies directed at improving or arresting cellular GSSG clearance may be effective in minimizing oxidative stress-related tissue injury or potentiating the killing of tumor cells, respectively. ..
  58. Cai Y, Kumar R, Zhou J, Foster P, Webb D. Ym1/2 promotes Th2 cytokine expression by inhibiting 12/15(S)-lipoxygenase: identification of a novel pathway for regulating allergic inflammation. J Immunol. 2009;182:5393-9 pubmed publisher
    ..In summary, our results suggest that production of Ym1/2 in response to IL-13 promotes Th2 cytokine production and allergic airways inflammation by inhibiting the production of 12(S)-HETE by 12/15-LOX. ..
  59. 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...
  60. Lee G, Cantor R, Abnoosian A, Park E, Yamamoto M, Hovland D, et al. A gene(s) for all-trans-retinoic acid-induced forelimb defects mapped and confirmed to murine chromosome 11. Genetics. 2005;170:345-53 pubmed
    ..The human syntenic region of this locus has been previously linked to Meckel syndrome; the phenotype includes postaxial polydactyly, an ectopic digital defect hypothesized to be induced by a common molecular pathway with ectrodactyly. ..
  61. Ibrahim A, Saleh H, El Shafey M, Hussein K, El Masry K, Baban B, et al. Targeting of 12/15-Lipoxygenase in retinal endothelial cells, but not in monocytes/macrophages, attenuates high glucose-induced retinal leukostasis. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862:636-645 pubmed publisher
    ..This may facilitate the development of more precisely targeted treatment strategies for DR. ..
  62. 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. ..
  63. Chattopadhyay R, Tinnikov A, Dyukova E, Singh N, Kotla S, Mobley J, et al. 12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction. J Lipid Res. 2015;56:562-77 pubmed publisher
    ..These observations provide novel insights on the role of XO in 12/15-LO-induced JamA tyrosine phosphorylation and TJ disruption leading to increased vascular permeability in response to HFD. ..
  64. Jang I, Park S, Cho J, Yigitkanli K, van Leyen K, Roth J. Genetic ablation and short-duration inhibition of lipoxygenase results in increased macroautophagy. Exp Cell Res. 2014;321:276-87 pubmed publisher
    ..Nonetheless, it is unclear what the consequences are of abolishing 12/15-LOX activity. Mice in which the alox15 gene has been ablated do not show an obvious phenotype, and LOX enzyme inhibition is not overtly detrimental...
  65. Song L, Yang H, Wang H, Tian C, Liu Y, Zeng X, et al. Inhibition of 12/15 lipoxygenase by baicalein reduces myocardial ischemia/reperfusion injury via modulation of multiple signaling pathways. Apoptosis. 2014;19:567-80 pubmed publisher
    ..Our data indicated that 12/15-LOX inhibitor baicalein can prevent myocardial I/R injury by modulation of multiple mechanisms, and suggest that baicalein could represent a novel therapeutic drug for acute myocardial infarction. ..
  66. Moore K, Lovercamp K, Feng D, Antelman J, Sutovsky M, Manandhar G, et al. Altered epididymal sperm maturation and cytoplasmic droplet migration in subfertile male Alox15 mice. Cell Tissue Res. 2010;340:569-81 pubmed publisher
    ..of the organelle degradation enzyme 15-lipoxygenase (15LOX) in sperm CD, we hypothesize that subfertile male Alox15 mice lacking the 15Lox gene display sperm CD anomalies...
  67. Morita M, Kuba K, Ichikawa A, Nakayama M, Katahira J, Iwamoto R, et al. The lipid mediator protectin D1 inhibits influenza virus replication and improves severe influenza. Cell. 2013;153:112-25 pubmed publisher
    ..These results identify the endogenous lipid mediator PD1 as an innate suppressor of influenza virus replication that protects against lethal influenza virus infection. ..
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    ..These results demonstrate that EGF-stimulated epithelial wound healing is partially mediated through a 12/15-LOX-LXA4 pathway, and activation of ERK1/2 and p38 is required for LXA4 action. ..
  69. 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. ..
  70. Matsushita M, Freigang S, Schneider C, Conrad M, Bornkamm G, Kopf M. T cell lipid peroxidation induces ferroptosis and prevents immunity to infection. J Exp Med. 2015;212:555-68 pubmed publisher
    ..Ex vivo, Gpx4-deficient T cells rapidly accumulated membrane lipid peroxides and concomitantly underwent cell death driven by ferroptosis but not necroptosis. These studies unveil an essential role of Gpx4 for T cell immunity. ..
  71. Cole B, Morris M, Grzesik W, Leone K, Nadler J. Adipose tissue-specific deletion of 12/15-lipoxygenase protects mice from the consequences of a high-fat diet. Mediators Inflamm. 2012;2012:851798 pubmed publisher
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    ..12/15-LO is an important mediator of VSMC growth. The growth-promoting effects of 12/15-LO are at least partially mediated through induction of Id3 transcription. ..
  74. Wu M, Lin T, Chiu Y, Liou H, Yang R, Fu W. Involvement of 15-lipoxygenase in the inflammatory arthritis. J Cell Biochem. 2012;113:2279-89 pubmed publisher
    ..15-LOX is thus a good target for developing drugs in the treatment of inflammatory arthritis. ..