Gene Symbol: ALOX12
Description: arachidonate 12-lipoxygenase, 12S type
Alias: 12-LOX, 12S-LOX, LOG12, arachidonate 12-lipoxygenase, 12S-type, 12S-lipoxygenase, lipoxin synthase 12-LO, platelet 12-LOX, platelet-type 12-lipoxygenase, platelet-type lipoxygenase 12
Species: human
Products:     ALOX12

Top Publications

  1. Jiang W, Douglas Jones A, Mansel R. Levels of expression of lipoxygenases and cyclooxygenase-2 in human breast cancer. Prostaglandins Leukot Essent Fatty Acids. 2003;69:275-81 pubmed
  2. Coffey M, Jarvis G, Gibbins J, Coles B, Barrett N, Wylie O, et al. Platelet 12-lipoxygenase activation via glycoprotein VI: involvement of multiple signaling pathways in agonist control of H(P)ETE synthesis. Circ Res. 2004;94:1598-605 pubmed
  3. Nie D, Krishnamoorthy S, Jin R, Tang K, Chen Y, Qiao Y, et al. Mechanisms regulating tumor angiogenesis by 12-lipoxygenase in prostate cancer cells. J Biol Chem. 2006;281:18601-9 pubmed
  4. Goodman J, Bowman E, Chanock S, Alberg A, Harris C. Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk. Carcinogenesis. 2004;25:2467-72 pubmed ALOX and COX genes have been identified, including G-1752A, G-1699A and Glu254Lys in ALOX5; Gln261Arg in ALOX12; Leu237Met and Val481Ile in COX1; and C-645T and Val511Ala in COX2...
  5. Mullin B, Spector T, Curtis C, Ong G, Hart D, Hakim A, et al. Polymorphisms in ALOX12, but not ALOX15, are significantly associated with BMD in postmenopausal women. Calcif Tissue Int. 2007;81:10-7 pubmed
    ..significant sequence homology with the murine Alox15 gene; however, the human arachidonate 12-lipoxygenase gene (ALOX12) is functionally more similar to the mouse gene...
  6. Aleem A, Jankun J, Dignam J, Walther M, Kuhn H, Svergun D, et al. Human platelet 12-lipoxygenase, new findings about its activity, membrane binding and low-resolution structure. J Mol Biol. 2008;376:193-209 pubmed
  7. Singh A, Kant S, Parshad R, Banerjee N, Dey S. Evaluation of human LOX-12 as a serum marker for breast cancer. Biochem Biophys Res Commun. 2011;414:304-8 pubmed publisher
    ..0001) reduction of LOX-12 levels after chemotherapy. This was also confirmed by ELISA. This study for the first time had co-related the quantity of serum LOX-12 with breast cancer and also with the effect of chemotherapy. ..
  8. Yoshimura R, Matsuyama M, Tsuchida K, Kawahito Y, Sano H, Nakatani T. Expression of lipoxygenase in human bladder carcinoma and growth inhibition by its inhibitors. J Urol. 2003;170:1994-9 pubmed
    ..Results suggest that lipoxygenase inhibitors may mediate potent antiproliferative effects against bladder cancer cells. Thus, lipoxygenase may become a new target in the treatment of bladder tumors. ..
  9. 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. ..

More Information

Publications159 found, 100 shown here

  1. Quintana L, Guzman B, Collado S, Claria J, Poch E. A coding polymorphism in the 12-lipoxygenase gene is associated to essential hypertension and urinary 12(S)-HETE. Kidney Int. 2006;69:526-30 pubmed
    ..acid-derived metabolite 12-(S)hydroxyeicosatetraenoic acid (12(S)-HETE), catalyzed by 12-lipoxygenase (12-LOX, ALOX12), exhibits a variety of biological activities with implications in cardiovascular disease...
  2. Tan W, Wu J, Zhang X, Guo Y, Liu J, Sun T, et al. Associations of functional polymorphisms in cyclooxygenase-2 and platelet 12-lipoxygenase with risk of occurrence and advanced disease status of colorectal cancer. Carcinogenesis. 2007;28:1197-201 pubmed
    ..38, 95% CI = 1.09-1.74). Together, these observations indicate that inherited polymorphisms in arachidonic acid-metabolizing enzymes may confer susceptibility to CRC. ..
  3. Mohammad A, Abdel H, Abdel W, Ahmed A, Wael T, Eiman G. Expression of cyclooxygenase-2 and 12-lipoxygenase in human breast cancer and their relationship with HER-2/neu and hormonal receptors: impact on prognosis and therapy. Indian J Cancer. 2006;43:163-8 pubmed
    ..Furthermore, there is an inverse association between cox-2 expression and hormonal receptor status. This observation may drive us to the possible role of those two enzymes in determining the plan of therapy of breast cancer patients. ..
  4. Yin B, Yang Y, Zhao Z, Zeng Y, Mooney S, Li M, et al. Arachidonate 12-lipoxygenase may serve as a potential marker and therapeutic target for prostate cancer stem cells. Int J Oncol. 2011;38:1041-6 pubmed publisher
    ..However, no 12-LOX was detected in normal prostate epithelial SCs in normal prostate tissue samples. These multiple lines of evidence support the possibility that 12-LOX may serve as a unique marker and therapeutic target for PCa SCs. ..
  5. Gohara A, Eltaki N, Sabry D, Murtagh D, Jankun J, Selman S, et al. Human 5-, 12- and 15-lipoxygenase-1 coexist in kidney but show opposite trends and their balance changes in cancer. Oncol Rep. 2012;28:1275-82 pubmed publisher
    ..Thus, it may be valuable to probe 12S-LOX activity and monitor its natural metabolite to seek a possible aid in directing the treatment of patients. ..
  6. Yoshimoto T, Yamamoto Y, Arakawa T, Suzuki H, Yamamoto S, Yokoyama C, et al. Molecular cloning and expression of human arachidonate 12-lipoxygenase. Biochem Biophys Res Commun. 1990;172:1230-5 pubmed
    ..The cytosol of Escherichia coli transformed with a recombinant pUC19 plasmid oxygenated the position 12 of arachidonic acid. ..
  7. Nie D, Hillman G, Geddes T, Tang K, Pierson C, Grignon D, et al. Platelet-type 12-lipoxygenase in a human prostate carcinoma stimulates angiogenesis and tumor growth. Cancer Res. 1998;58:4047-51 pubmed
    ..These data indicate that 12-LOX stimulates human PCa tumor growth by a novel angiogenic mechanism. ..
  8. Nie D, Nemeth J, Qiao Y, Zacharek A, Li L, Hanna K, et al. Increased metastatic potential in human prostate carcinoma cells by overexpression of arachidonate 12-lipoxygenase. Clin Exp Metastasis. 2003;20:657-63 pubmed
    ..Taken together, our data suggest that an increase in 12-LOX expression enhances the metastatic potential of human prostate cancer cells. ..
  9. Matsuyama M, Yoshimura R, Mitsuhashi M, Hase T, Tsuchida K, Takemoto Y, et al. Expression of lipoxygenase in human prostate cancer and growth reduction by its inhibitors. Int J Oncol. 2004;24:821-7 pubmed
    ..LOX is induced in prostate cancer, and our results suggest that LOX inhibitors may mediate potent antiproliferative effects against prostate cancer cells. Thus, LOX may become a new target in treatment of prostate cancer. ..
  10. Ichikawa S, Koller D, Johnson M, Lai D, Xuei X, Edenberg H, et al. Human ALOX12, but not ALOX15, is associated with BMD in white men and women. J Bone Miner Res. 2006;21:556-64 pubmed
    The Alox15 gene was recently identified as a negative regulator of peak BMD in mice. Polymorphisms in human ALOX12, but not ALOX15, were significantly associated with spine BMD in white men and women, suggesting that ALOX12 may contribute ..
  11. Gong Z, Hebert J, Bostick R, Deng Z, Hurley T, Dixon D, et al. Common polymorphisms in 5-lipoxygenase and 12-lipoxygenase genes and the risk of incident, sporadic colorectal adenoma. Cancer. 2007;109:849-57 pubmed
    ..Further studies will be needed to confirm these findings. Cancer 2007 (c) 2007 American Cancer Society. ..
  12. 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. ..
  13. Liu Q, Tan W, Che J, Yuan D, Zhang L, Sun Y, et al. 12-HETE facilitates cell survival by activating the integrin-linked kinase/NF-κB pathway in ovarian cancer. Cancer Manag Res. 2018;10:5825-5838 pubmed publisher
    ..These results indicate that 12-HETE participates in the inhibition of cell apoptosis by activating the ILK/NF-κB pathway, implying an important underlying mechanism that promotes the survival of ovarian cancer cells. ..
  14. Doucet M, Jougleux J, Poirier S, Cormier M, Leger J, Surette M, et al. Identification of peracetylated quercetin as a selective 12-lipoxygenase pathway inhibitor in human platelets. Mol Pharmacol. 2018;: pubmed publisher
  15. Chu B, Kon N, Chen D, Li T, Liu T, Jiang L, et al. ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway. Nat Cell Biol. 2019;: pubmed publisher
    ..Instead, ALOX12 inactivation diminishes p53-mediated ferroptosis induced by reactive oxygen species stress and abrogates p53-..
  16. Aiken C, Tarry Adkins J, Ashmore T, Ozanne S. Early life environment influences the trajectory of post-partum weight loss in adult female rats. Reprod Biomed Online. 2019;38:779-786 pubmed publisher
    ..01) than controls. Post-partum recuperated animals also had increased expression of IL6, NRF2 and ALOX12 (key regulators of inflammation and lipoxygenase activity) in the intra-abdominal adipose tissue compared with ..
  17. Reddy K, Vidya Rajan V, Gupta A, Aparoy P, Reddanna P. Exploration of binding site pattern in arachidonic acid metabolizing enzymes, Cyclooxygenases and Lipoxygenases. BMC Res Notes. 2015;8:152 pubmed publisher
    ..Comparisons in various combinations showed how they are similar and dissimilar with each other. This information will be helpful in designing specific as well as common inhibitors. ..
  18. Dalli J, Zhu M, Vlasenko N, Deng B, Haeggstrom J, Petasis N, et al. The novel 13S,14S-epoxy-maresin is converted by human macrophages to maresin 1 (MaR1), inhibits leukotriene A4 hydrolase (LTA4H), and shifts macrophage phenotype. FASEB J. 2013;27:2573-83 pubmed publisher
  19. Ito H, Otsuki A, Mori H, Li P, Kinoshita M, Kawakami Y, et al. Two new monoterpene glycosides from Qing Shan Lu Shui tea with inhibitory effects on leukocyte-type 12-lipoxygenase activity. Molecules. 2013;18:4257-66 pubmed publisher
    ..Ligurosides A (1) and B (2) showed inhibitory effects on leukocyte-type 12-LOX activity, with IC50 values of 1.7 and 0.7 μM, respectively. ..
  20. Lovat P, Ranalli M, Corazzari M, Raffaghello L, Pearson A, Ponzoni M, et al. Mechanisms of free-radical induction in relation to fenretinide-induced apoptosis of neuroblastoma. J Cell Biochem. 2003;89:698-708 pubmed
    ..The targeting of 12-LOX in neuroblastoma cells may thus be a novel pathway for the development of drugs inducing apoptosis of neuroblastoma with improved tumor specificity. ..
  21. McDonnell M, Li H, Funk C. Characterization of epidermal 12(S) and 12(R) lipoxygenases. Adv Exp Med Biol. 2002;507:147-53 pubmed
  22. Ha J, Dho S, Youm T, Kwon K, Park S. Astrocytic phospholipase A2 contributes to neuronal glutamate toxicity. Brain Res. 2014;1590:97-106 pubmed publisher
    ..These findings suggest that astrocytic PLA2 activity increases neuronal sensitivity to chronic glutamate exposure in neuron-astrocyte co-cultures. ..
  23. Dadaian M, Westlund P. Substrate down regulation of 12-lipoxygenase in human platelets. Adv Exp Med Biol. 2002;507:113-6 pubmed
  24. Coffey M, Coles B, Locke M, Bermudez Fajardo A, Williams P, Jarvis G, et al. Interactions of 12-lipoxygenase with phospholipase A2 isoforms following platelet activation through the glycoprotein VI collagen receptor. FEBS Lett. 2004;576:165-8 pubmed
    ..This study shows that platelet 12-H(P)ETE generation utilizes arachidonate substrate from both c- and sPLA2 and that 12-LOX functionally associates with both PLA2 isoforms. ..
  25. Liu P, Lu Y, Recker R, Deng H, Dvornyk V. ALOX12 gene is associated with the onset of natural menopause in white women. Menopause. 2010;17:152-6 pubmed publisher
    ..This study investigated the ALOX12 gene for its possible association with ANM...
  26. Massanella M, Singhania A, Beliakova Bethell N, Pier R, Lada S, White C, et al. Differential gene expression in HIV-infected individuals following ART. Antiviral Res. 2013;100:420-8 pubmed publisher
    ..g., ALOX12 and CYP2S1). Targets not confirmed by RT-qPCR (i.e...
  27. Silva C, Biselli Périco J, Zampieri B, Silva W, de Souza J, Bürger M, et al. Differential Expression of Inflammation-Related Genes in Children with Down Syndrome. Mediators Inflamm. 2016;2016:6985903 pubmed publisher
    ..Twenty genes showed differential expression in children with DS; 12 were overexpressed (PLA2G2D, CACNA1D, ALOX12, VCAM1, ICAM1, PLCD1, ADRB1, HTR3A, PDE4C, CASP1, PLA2G5, and PLCB4), and eight were underexpressed (LTA4H, BDKRB1,..
  28. Kutzner L, Goloshchapova K, Heydeck D, Stehling S, Kuhn H, Schebb N. Mammalian ALOX15 orthologs exhibit pronounced dual positional specificity with docosahexaenoic acid. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862:666-675 pubmed publisher
    ..Here we expressed the ALOX15 orthologs of eight different mammalian species as well as human ALOX12 and ALOX15B as recombinant his-tag fusion proteins and characterized their reaction specificity with the most ..
  29. Zglejc Waszak K, Waszkiewicz E, Franczak A. Periconceptional undernutrition affects the levels of DNA methylation in the peri-implantation pig endometrium and in embryos. Theriogenology. 2019;123:185-193 pubmed publisher
    ..adiponectin receptor 2 (ADIPOR2), prostaglandin-endoperoxide synthase 2 (PTGS2), arachidonate 12-lipoxygenase (ALOX12), progestin and adipoQ receptor family member 7 (PAQR7), progesterone receptor membrane component 2 (PGRMC2), ..
  30. Roumeliotis A, Roumeliotis S, Panagoutsos S, Tsetsos F, Georgitsi M, Manolopoulos V, et al. Association of ALOX12 gene polymorphism with all-cause and cardiovascular mortality in diabetic nephropathy. Int Urol Nephrol. 2018;50:321-329 pubmed publisher
    ..The aim of the study is to clarify a potential ALOX12 role in CVD presence and progress of diabetic patients in different stages of nephropathy...
  31. Paul K, Chuang Y, Cockburn M, Bronstein J, Horvath S, Ritz B. Organophosphate pesticide exposure and differential genome-wide DNA methylation. Sci Total Environ. 2018;645:1135-1143 pubmed publisher
    ..We identified 70 genome-wide significant CpGs, including cg01600516 in ALOX12 (cor = 0.27, p = 1.73E-11) and two CpGs in HLA genes, cg01655658 (cor = -0.24, p = 2...
  32. De Armas R, Durand K, Guillaudeau A, Weinbreck N, Robert S, Moreau J, et al. mRNA levels of enzymes and receptors implicated in arachidonic acid metabolism in gliomas. Clin Biochem. 2010;43:827-35 pubmed publisher
    ..mRNA levels of enzymes and receptors implicated both in lipoxygenase and cyclooxygenase pathways differed significantly in gliomas according to the histological type. ..
  33. Maloberti P, Duarte A, Orlando U, Pasqualini M, Solano A, Lopez Otin C, et al. Functional interaction between acyl-CoA synthetase 4, lipooxygenases and cyclooxygenase-2 in the aggressive phenotype of breast cancer cells. PLoS ONE. 2010;5:e15540 pubmed publisher
    ..Therefore, the development of combinatory therapies that profit from the ACSL4, lipooxygenase and COX-2 synergistic action may allow for lower medication doses and avoidance of side effects. ..
  34. Mucaji P, Záhradníková A, Bezakova L, Cupáková M, Rauová D, Nagy M. HPLC determination of antilipoxygenase activity of a water infusion of Ligustrum vulgare L. leaves and some of its constituents. Molecules. 2011;16:8198-208 pubmed publisher
    ..Echinacoside was ineffective against LOXs in lower concentrations, while higher concentration showed similar inhibition on 8-LOX and 12-LOX. 15-LOX was affected more and the presence of echinacoside remarkably decreased its activity. ..
  35. Grzesik W, Nadler J, Machida Y, Nadler J, Imai Y, Morris M. Expression pattern of 12-lipoxygenase in human islets with type 1 diabetes and type 2 diabetes. J Clin Endocrinol Metab. 2015;100:E387-95 pubmed publisher
    ..The costaining of PP and vimentin suggests that 12-LO participates in the process leading to β-cell dedifferentiation in the islet. ..
  36. Schuchardt J, Ostermann A, Stork L, Fritzsch S, Kohrs H, Greupner T, et al. Effect of DHA supplementation on oxylipin levels in plasma and immune cell stimulated blood. Prostaglandins Leukot Essent Fatty Acids. 2017;121:76-87 pubmed publisher
    ..We demonstrated that DHA supplementation causes a time-dependent shift in the entire oxylipin profile suggesting a cross-linked metabolism of PUFAs and subsequent formation of oxygenated lipid mediators. ..
  37. Segraves E, Holman T. Kinetic investigations of the rate-limiting step in human 12- and 15-lipoxygenase. Biochemistry. 2003;42:5236-43 pubmed
    ..The KIE could not be determined for 12-hLO due to its inability to efficiently catalyze LA, but the k(cat)/K(M) SIE was temperature-independent, indicating distinct rate-limiting steps from both 15-hLO and sLO-1. ..
  38. Figlioli G, Elisei R, Romei C, Melaiu O, Cipollini M, Bambi F, et al. A Comprehensive Meta-analysis of Case-Control Association Studies to Evaluate Polymorphisms Associated with the Risk of Differentiated Thyroid Carcinoma. Cancer Epidemiol Biomarkers Prev. 2016;25:700-13 pubmed publisher
    ..10 more SNPs within 9q22, six within FTO, two within SOD1, and single variations within HUS1, WDR3, UGT2B7, ALOX12, TICAM1, ATG16L1, HDAC4, PIK3CA, SULF1, IL11RA, VEGFA, and 1p31.3, 2q35, 8p12, and 14q13...
  39. Hada T, Ueda N, Takahashi Y, Yamamoto S. Catalytic properties of human platelet 12-lipoxygenase as compared with the enzymes of other origins. Biochim Biophys Acta. 1991;1083:89-93 pubmed
  40. Lebeau A, Terro F, Rostene W, Pelaprat D. Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by beta-amyloid peptide. Cell Death Differ. 2004;11:875-84 pubmed
    ..These data indicate that blockade of 12-LOX expression disrupts a c-Jun-dependent apoptosis pathway, and suggest that 12-LOX may represent a new target for the treatment of AD. ..
  41. Resler A, Makar K, Heath L, Whitton J, Potter J, Poole E, et al. Genetic variation in prostaglandin synthesis and related pathways, NSAID use and colorectal cancer risk in the Colon Cancer Family Registry. Carcinogenesis. 2014;35:2121-6 pubmed publisher
    ..adjustment for multiple comparisons, two intronic SNPs were associated with rectal cancer risk: rs11571364 in ALOX12 [OR(het/hzv) = 1.87, 95% confidence interval (CI) = 1.19-2.95, P = 0.03] and rs45525634 in PTGER2 (OR(het/hzv) = 0...
  42. Maskrey B, Rushworth G, Law M, Treweeke A, Wei J, Leslie S, et al. 12-hydroxyeicosatetraenoic acid is associated with variability in aspirin-induced platelet inhibition. J Inflamm (Lond). 2014;11:33 pubmed publisher
    ..The study also highlights a potentially important mechanism by which aspirin impacts upon eicosanoid generation. ..
  43. López Úbeda R, García Vázquez F, Romar R, Gadea J, Muñoz M, Hunter R, et al. Oviductal Transcriptome Is Modified after Insemination during Spontaneous Ovulation in the Sow. PLoS ONE. 2015;10:e0130128 pubmed publisher
    ..pre-implantation embryos (C3, IGHG1, ITIH4, TNF and SERPINE1) whereas others were not previously reported (SAA2, ALOX12, CD1D and SPP1)...
  44. Lenkiewicz A, Czapski G, Jesko H, Wilkaniec A, Szypuła W, Pietrosiuk A, et al. Potent effects of alkaloid-rich extract from Huperzia selago against sodium nitroprusside-evoked PC12 cells damage via attenuation of oxidative stress and apoptosis. Folia Neuropathol. 2016;54:156-66 pubmed
    ..Ifng) and cyclooxygenase 2 (Ptgs2) as well as significantly down-regulated the expression of 12/15-lipoxygenase (Alox12) and tended to decrease the mRNA level of interleukin-6 gene (Il6)...
  45. Srikanth M, Chandrasaharan K, Zhao X, Chayaburakul K, Ong W, Herr D. Metabolism of Docosahexaenoic Acid (DHA) Induces Pyroptosis in BV-2 Microglial Cells. Neuromolecular Med. 2018;20:504-514 pubmed publisher
    ..Cumulatively, these data demonstrate that DHA has an anti-inflammatory effect on microglial cells, but its metabolism by 12-LOX generates one or more products that activate a proinflammatory cell death program. ..
  46. Yu Z, Schneider C, Boeglin W, Brash A. Human and mouse eLOX3 have distinct substrate specificities: implications for their linkage with lipoxygenases in skin. Arch Biochem Biophys. 2006;455:188-96 pubmed
    ..The substrate preference of mouse eLOX3 and the unique occurrence of an 8S-LOX enzyme in mouse skin point to a potential LOX pathway for the production of epoxyalcohol in murine epidermal differentiation. ..
  47. Connor A, Baumgartner R, Baumgartner K, Pinkston C, Boone S, John E, et al. Associations between ALOX, COX, and CRP polymorphisms and breast cancer among Hispanic and non-Hispanic white women: The breast cancer health disparities study. Mol Carcinog. 2015;54:1541-53 pubmed publisher
    ..01). Two-way interactions with NA ancestry (P(adj)  < 0.05) were observed for ALOX12 (rs2292350, rs2271316) and PTGS1 (rs10306194)...
  48. Meka B, Ravada S, Murali Krishna Kumar M, Purna Nagasree K, Golakoti T. Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities. Bioorg Med Chem. 2017;25:1374-1388 pubmed publisher
    ..Our study found potentiating effects of 2-formyl and 3-keto substituents in reviving inactive AKBA analogues possessing essential COOH group at 4th position. ..
  49. Liu Y, Freedman B, Burdon K, Langefeld C, Howard T, Herrington D, et al. Association of arachidonate 12-lipoxygenase genotype variation and glycemic control with albuminuria in type 2 diabetes. Am J Kidney Dis. 2008;52:242-50 pubmed publisher
    ..5% (uncontrolled type 2 diabetes mellitus). Four haplotype-tagging variants in the arachidonate 12LO gene (ALOX12), glycemic control, and other covariates. Albuminuria measured by means of urinary albumin-creatinine ratio (ACR)...
  50. Cavallo J, Hamilton B, Farley J. In vitro extinction learning in Hermissenda: involvement of conditioned inhibition molecules. Front Behav Neurosci. 2014;8:354 pubmed publisher
  51. Chien Y, Chou S, Chang Y, Leu H, Yang Y, Tsai P, et al. Inhibition of Arachidonate 12/15-Lipoxygenase Improves ?-Galactosidase Efficacy in iPSC-Derived Cardiomyocytes from Fabry Patients. Int J Mol Sci. 2018;19: pubmed publisher
    ..The proteomic analysis revealed that arachidonate 12/15-lipoxygenase (Alox12/15) was the most highly upregulated marker in FC-iPSC-CMs, and the metabolites of Alox12/15, 12(S)- and 15(S)-..
  52. Winer I, Normolle D, Shureiqi I, Sondak V, Johnson T, Su L, et al. Expression of 12-lipoxygenase as a biomarker for melanoma carcinogenesis. Melanoma Res. 2002;12:429-34 pubmed
    ..01). These data suggest that 12-LOX may be an important novel marker for cancer progression within the melanoma system, and therefore could be a useful biomarker and therapeutic target for melanoma chemoprevention. ..
  53. Tourdot B, Holinstat M. Targeting 12-Lipoxygenase as a Potential Novel Antiplatelet Therapy. Trends Pharmacol Sci. 2017;38:1006-1015 pubmed publisher
    ..While published data suggests targeting 12-LOX is a viable approach, further work is required to determine the safety and effectiveness of 12-LOX inhibitors in humans. ..
  54. Franczak A, Zglejc Waszak K, Martyniak M, Waszkiewicz E, Kotwica G. Peri-conceptional nutritional restriction alters transcriptomic profile in the peri-implantation pig embryos. Anim Reprod Sci. 2018;197:305-316 pubmed publisher
    ..high mobility group box 2 (HMGB2), prostaglandin-endoperoxide synthase 2 (PTGS2), arachidonate 12-lipoxygenase (ALOX12), adiponectin receptor 2 (ADIPOR2), DNA (cytosine-5)-methyltransferase 1 (DNMT1), steroidogenic acute regulatory ..
  55. Funk C, Funk L, Fitzgerald G, Samuelsson B. Characterization of human 12-lipoxygenase genes. Proc Natl Acad Sci U S A. 1992;89:3962-6 pubmed
    ..There was no detectable 12-lipoxygenase gene 2 expression in several tissues and cell lines. ..
  56. Hagmann W, Gao X, Timar J, Chen Y, Strohmaier A, Fahrenkopf C, et al. 12-Lipoxygenase in A431 cells: genetic identity, modulation of expression, and intracellular localization. Exp Cell Res. 1996;228:197-205 pubmed
    ..Further, the basal expression of 12-lipoxygenase depends on signal pathways requiring protein tyrosine kinase activity, since genistein, herbimycin A, and tyrphostin 25 reduce the expression of 12-lipoxygenase protein in A431 cells. ..
  57. Gu J, Wen Y, Mison A, Nadler J. 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. Endocrinology. 2003;144:534-43 pubmed
    ..These results suggest that 12-LO stimulation leads to aldosterone production in H295R cells in part through activation of CREB/ATF-1 and p38 MAPK pathway. ..
  58. Fridman C, Ojopi E, Gregorio S, Ikenaga E, Moreno D, Demetrio F, et al. Association of a new polymorphism in ALOX12 gene with bipolar disorder. Eur Arch Psychiatry Clin Neurosci. 2003;253:40-3 pubmed
    ..Using DNA sequencing we could confirm a new non-synonymous SNP in the conservative domain of the ALOX12 gene (17p13.1), suggested by EST alignment...
  59. Rosiak M, Postula M, Kaplon Cieslicka A, Kondracka A, Trzepla E, Zaremba M, et al. Lack of effect of common single nucleotide polymorphisms in leukotriene pathway genes on platelet reactivity in patients with diabetes. Mol Med Rep. 2013;8:853-60 pubmed publisher
    ..The results of our study suggest that certain polymorphisms of the LT pathway are not associated with altered platelet reactivity and the measured LTs in diabetic patients treated with ASA. ..
  60. Ibrahim A, Elshafey S, Sellak H, Hussein K, El Sherbiny M, Abdelsaid M, et al. A lipidomic screen of hyperglycemia-treated HRECs links 12/15-Lipoxygenase to microvascular dysfunction during diabetic retinopathy via NADPH oxidase. J Lipid Res. 2015;56:599-611 pubmed publisher
    ..In vitro experiments also showed that 15-HETE induced HREC migration and tube formation in a NOX-dependent manner. Taken together our data suggest that 12/15-LOX is implicated in DR via a NOX-dependent mechanism. ..
  61. Nakamura M, Ueda N, Kishimoto K, Yoshimoto T, Yamamoto S, Ishimura K. Immunocytochemical localization of platelet-type arachidonate 12-lipoxygenase in mouse blood cells. J Histochem Cytochem. 1995;43:237-44 pubmed
    ..These results indicated the expression of 12-lipoxygenase at an early stage in the course of megakaryocytopoiesis. ..
  62. Jacquot C, Wecksler A, McGinley C, Segraves E, Holman T, van der Donk W. Isotope sensitive branching and kinetic isotope effects in the reaction of deuterated arachidonic acids with human 12- and 15-lipoxygenases. Biochemistry. 2008;47:7295-303 pubmed publisher
    ..Smaller but clear changes in regioselectivity were also observed for 12-hLO and 15-hLO-2. ..
  63. Skrzypczak Jankun E, Jankun J, al Senaidy A. Human lipoxygenase: developments in its structure, function, relevance to diseases and challenges in drug development. Curr Med Chem. 2012;19:5122-7 pubmed
    ..iv) Allosteric mechanism might involve orchestrated conformational changes and flexibility of the coils connecting the structured elements and ligands binding in more than one monomer. ..
  64. Wecksler A, Jacquot C, van der Donk W, Holman T. Mechanistic investigations of human reticulocyte 15- and platelet 12-lipoxygenases with arachidonic acid. Biochemistry. 2009;48:6259-67 pubmed publisher
    ..3 s(-1) microM(-1)). Considering that the oxygen concentration in cancerous tissue can be less than 5 microM, this result may have cellular implications with respect to the substrate specificity of 15-hLO-1. ..
  65. Mascayano C, Espinosa V, Sepúlveda Boza S, Hoobler E, Perry S, Diaz G, et al. Enzymatic Studies of Isoflavonoids as Selective and Potent Inhibitors of Human Leukocyte 5-Lipo-Oxygenase. Chem Biol Drug Des. 2015;86:114-21 pubmed publisher
  66. Flatman S, Morgan A, McDonald Gibson R, Davey A, Jonas G, Slater T. 12-Lipoxygenase activity in human uterine cervix. Prostaglandins Leukot Essent Fatty Acids. 1988;32:87-94 pubmed
    ..However activity was significantly lower in samples taken from post-menopausal patients compared with pre-menopausal patients. ..
  67. Xiao W, Ke Y, He J, Zhang H, Yu J, Hu W, et al. Association of ALOX12 and ALOX15 gene polymorphisms with age at menarche and natural menopause in Chinese women. Menopause. 2012;19:1029-36 pubmed publisher
    ..In this study, we investigated the possible association of two key gene (ALOX12 and ALOX15) polymorphisms with age of menarche and menopause in Chinese women...
  68. Chang J, Jiang L, Wang Y, Yao B, Yang S, Zhang B, et al. 12/15 Lipoxygenase regulation of colorectal tumorigenesis is determined by the relative tumor levels of its metabolite 12-HETE and 13-HODE in animal models. Oncotarget. 2015;6:2879-88 pubmed
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    ..i>Cnr2, and Trpv1), endocannabinoid degradation enzymes (Faah, Ptgs2, and Alox12), and TRPV1 sensitizing kinases (Mapk3, Mapk14, Prkcg, and Prkaca)...
  71. Garcia C, Lamarque A, Comba A, Berra M, Silva R, Labuckas D, et al. Synergistic anti-tumor effects of melatonin and PUFAs from walnuts in a murine mammary adenocarcinoma model. Nutrition. 2015;31:570-7 pubmed publisher
    ..0001). COX-[12(S)-HHT] was lower and 12 LOX-[12(S)-HETE] was higher in TCs from the MD group than form the WD and CD arms (P < 0.05)...
  72. Xiao W, Ke Y, He J, Zhang H, Yu J, Hu W, et al. Polymorphisms in the human ALOX12 and ALOX15 genes are associated with peak bone mineral density in Chinese nuclear families. Osteoporos Int. 2012;23:1889-97 pubmed publisher
    Association between ten single-nucleotide polymorphisms (SNPs) in the human ALOX12 and ALOX15 genes and variations in peak bone mineral density (BMD) in a large sample of Chinese nuclear families with female offspring using the ..
  73. Dilly A, Ekambaram P, Guo Y, Cai Y, Tucker S, Fridman R, et al. Platelet-type 12-lipoxygenase induces MMP9 expression and cellular invasion via activation of PI3K/Akt/NF-?B. Int J Cancer. 2013;133:1784-91 pubmed publisher
    ..The role of 12-LOX-mediated MMP9 secretion in endothelial cell migration may account for the proangiogenic function of 12-LOX in prostate cancer. ..
  74. Adili R, Tourdot B, Mast K, Yeung J, Freedman J, Green A, et al. First Selective 12-LOX Inhibitor, ML355, Impairs Thrombus Formation and Vessel Occlusion In Vivo With Minimal Effects on Hemostasis. Arterioscler Thromb Vasc Biol. 2017;37:1828-1839 pubmed publisher
    ..Our data strongly support 12-LOX as a key determinant of platelet reactivity in vivo, and inhibition of platelet 12-LOX with ML355 may represent a new class of antiplatelet therapy. ..
  75. Kroschwald S, Chiu C, Heydeck D, Rohwer N, Gehring T, Seifert U, et al. Female mice carrying a defective Alox15 gene are protected from experimental colitis via sustained maintenance of the intestinal epithelial barrier function. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863:866-880 pubmed publisher
    ..Since exogenous 12-HETE compromises the expression of the tight junction protein ZO-1 the protective effect has been related to a less pronounced impairment of the intestinal epithelial barrier function. ..
  76. 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. ..
  77. Bader A, Giner R, Martini F, Schinella G, Rios J, Braca A, et al. Modulation of COX, LOX and NF?B activities by Xanthium spinosum L. root extract and ziniolide. Fitoterapia. 2013;91:284-289 pubmed publisher
    ..Both the plant extract and ziniolide are in vitro inhibitors of the phorbol-induced NF?B activation, a key regulator of the arachidonic pathway. ..
  78. Bhowmick R, Clark S, Bonventre J, Leong J, McCormick B. Cytosolic Phospholipase A2α Promotes Pulmonary Inflammation and Systemic Disease during Streptococcus pneumoniae Infection. Infect Immun. 2017;85: pubmed publisher
    ..Our data suggest that cPLA2α plays a crucial role in eliciting pulmonary inflammation during pneumococcal infection and is required for lethal systemic infection following S. pneumoniae lung challenge. ..
  79. Zhang X, Cheng X, Yan Z, Fang J, Wang X, Wang W, et al. An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemia-reperfusion injury. Nat Med. 2017;: pubmed publisher
    ..Here, using integrative 'omics' analysis, we identified an arachidonate 12-lipoxygenase (ALOX12)-12-hydroxyeicosatetraenoic acid (12-HETE)-G-protein-coupled receptor 31 (GPR31) signaling axis as a key ..
  80. Wong P, Westlund P, Hamberg M, Granstrom E, Chao P, Samuelsson B. 15-Lipoxygenase in human platelets. J Biol Chem. 1985;260:9162-5 pubmed
    ..The present investigation thus demonstrates the occurrence of a 15-lipoxygenase in human platelets in addition to the previously known 12-lipoxygenase. ..
  81. Aleem A, Wells L, Jankun J, Walther M, Kuhn H, Reinartz J, et al. Human platelet 12-lipoxygenase: naturally occurring Q261/R261 variants and N544L mutant show altered activity but unaffected substrate binding and membrane association behavior. Int J Mol Med. 2009;24:759-64 pubmed
  82. Yang P, Cartwright C, Li J, Wen S, Prokhorova I, Shureiqi I, et al. Arachidonic acid metabolism in human prostate cancer. Int J Oncol. 2012;41:1495-503 pubmed publisher
    ..0.010 ng/mg protein, respectively; p=0.019). Our results suggest that LOX metabolites such as 12-HETE are critical in prostate cancer progression and that the LOX pathway may be a target for treating and preventing prostate cancer. ..
  83. Li S, Zhao X, Wu Z, Li Y, Zhu L, Cui B, et al. Polymorphisms in arachidonic acid metabolism-related genes and the risk and prognosis of colorectal cancer. Fam Cancer. 2013;12:755-65 pubmed publisher
    ..92, 95% CI 1.14-3.25, P(interaction) = 0.01). These observations indicate that 12-LOX 261Arg > Gln polymorphism may affect risk of rectal cancer, and it may be a potential predictive marker for prognosis of CRC. ..
  84. Yeung J, Apopa P, Vesci J, Stolla M, Rai G, Simeonov A, et al. 12-lipoxygenase activity plays an important role in PAR4 and GPVI-mediated platelet reactivity. Thromb Haemost. 2013;110:569-81 pubmed publisher
    ..Furthermore, the data presented here provide a basis for potentially targeting 12-LOX as a means to attenuate unwanted platelet activation and clot formation. ..
  85. Aliabadi A, Mohammadi Farani A, Hosseinzadeh Z, Nadri H, Moradi A, Ahmadi F. Phthalimide analogs as probable 15-lipoxygenase-1 inhibitors: synthesis, biological evaluation and docking studies. Daru. 2015;23:36 pubmed publisher
    ..The biological results of reported compounds in this research were not so satisfactory. But, further structural modifications are necessary to improve the bioactivity of these derivatives. ..
  86. Chai T, Cui F, Mu P, Yang Y, Xu N, Yin Z, et al. Enantio-alteration of gene transcription associated with bioconcentration in adult zebrafish (Danio rerio) exposed to chiral PCB149. Sci Rep. 2016;6:19478 pubmed publisher
    ..The strong positive correlations between expression levels of target genes (alox5a and alox12) and PCB149 bioconcentration suggest that prolonged exposure to the racemate of chiral PCB149 may result in ..
  87. Dilly A, Tang K, Guo Y, Joshi S, Ekambaram P, Maddipati K, et al. Convergence of eicosanoid and integrin biology: Role of Src in 12-LOX activation. Exp Cell Res. 2017;351:1-10 pubmed publisher
    ..Furthermore, we have shown that the 12-LOX activity modulated by these residues impacts migration. To our knowledge, this is the first report that c-Src kinase activity is required for β4-integrin-mediated phosphorylation of 12-LOX. ..
  88. Semeraro M, Glenn L, Morris M. The Four-Way Stop Sign: Viruses, 12-Lipoxygenase, Islets, and Natural Killer Cells in Type 1 Diabetes Progression. Front Endocrinol (Lausanne). 2017;8:246 pubmed publisher
    ..Furthermore, the human NK92 cell line expresses the ALOX12 protein [human 12-lipoxygenase (12-LO), related to mouse 12/15-LO] via Western blotting...
  89. Tornhamre S, Elmqvist A, Lindgren J. 15-Lipoxygenation of leukotriene A(4). Studies Of 12- and 15-lipoxygenase efficiency to catalyze lipoxin formation. Biochim Biophys Acta. 2000;1484:298-306 pubmed
  90. Klampfl T, Bogner E, Bednar W, Mager L, Massudom D, Kalny I, et al. Up-regulation of 12(S)-lipoxygenase induces a migratory phenotype in colorectal cancer cells. Exp Cell Res. 2012;318:768-78 pubmed publisher
    ..The results demonstrate that 12(S)-LOX expression in inflammatory areas of colorectal tumours has the capacity to induce an invasive phenotype in colorectal cancer cells and could be targeted for therapy. ..
  91. An J, Song Y, Kim K, Ko Y, Yoon D, Oh D. Biotransformation of polyunsaturated fatty acids to bioactive hepoxilins and trioxilins by microbial enzymes. Nat Commun. 2018;9:128 pubmed publisher
    ..These findings may facilitate physiological studies and drug development based on lipid mediators. ..
  92. Yoshimoto T, Arakawa T, Hada T, Yamamoto S, Takahashi E. Structure and chromosomal localization of human arachidonate 12-lipoxygenase gene. J Biol Chem. 1992;267:24805-9 pubmed
    ..The chromosomal localization of the human 12-lipoxygenase gene was examined by fluorescence in situ hybridization, and the gene was assigned to the sub-band p13.1 of chromosome 17. ..