Gene Symbol: Alox12
Description: arachidonate 12-lipoxygenase, 12S type
Alias: 12-LO, 12S-LOX, arachidonate 12-lipoxygenase, 12S-type, 12S-lipoxygenase, lipoxin synthase 12-LO, platelet 12-LOX, platelet-type lipoxygenase 12
Species: rat
Products:     Alox12

Top Publications

  1. 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. ..
  2. Gao X, Grignon D, Chbihi T, Zacharek A, Chen Y, Sakr W, et al. Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer. Urology. 1995;46:227-37 pubmed
    ..This enzyme also may be a novel target for the development of anti-invasive and antimetastatic agents. ..
  3. Tang D, Chen Y, Honn K. Arachidonate lipoxygenases as essential regulators of cell survival and apoptosis. Proc Natl Acad Sci U S A. 1996;93:5241-6 pubmed
    ..In contrast, p53, which is wild type in W256 cells, did not undergo alterations during apoptosis induction. The results suggest that the LOX pathway plays an important physiological role in regulating apoptosis. ..
  4. Chakrabarti S, Wen Y, Dobrian A, Cole B, Ma Q, Pei H, et al. Evidence for activation of inflammatory lipoxygenase pathways in visceral adipose tissue of obese Zucker rats. Am J Physiol Endocrinol Metab. 2011;300:E175-87 pubmed publisher
    ..In 3T3-L1 adipocytes, LSF abrogated the inflammatory response induced by LO products. Thus, therapeutic agents reducing LO or STAT4 activation may provide novel tools to reduce obesity-induced inflammation. ..
  5. Zhou W, Wang X, Kaduce T, Spector A, Lee H. Impaired arachidonic acid-mediated dilation of small mesenteric arteries in Zucker diabetic fatty rats. Am J Physiol Heart Circ Physiol. 2005;288:H2210-8 pubmed
    ..Increased oxidative stress and nitration of 12-lipoxygenase may underlie the impairment of AA-mediated relaxation in small mesenteric arteries of diabetic rats. ..
  6. Johnson E, Nanney L, Virmani J, Lawson J, Funk C. Basal transepidermal water loss is increased in platelet-type 12-lipoxygenase deficient mice. J Invest Dermatol. 1999;112:861-5 pubmed
    ..These results indicate that the platelet-type 12-lipoxygenase pathway in mice is partly responsible for normal permeability barrier function but the mechanism awaits further elucidation. ..
  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. Yoshimura R, Inoue K, Kawahito Y, Mitsuhashi M, Tsuchida K, Matsuyama M, et al. Expression of 12-lipoxygenase in human renal cell carcinoma and growth prevention by its inhibitor. Int J Mol Med. 2004;13:41-6 pubmed
    ..These results suggest 12-LOX may play a role in the progression of RCC in human tissue, and its inhibitors may become anticancer agents in human RCC. ..
  9. Lu M, Chen Y, Huang H, Ma M. Hypoxic preconditioning protects rat hearts against ischemia-reperfusion injury via the arachidonate12-lipoxygenase/transient receptor potential vanilloid 1 pathway. Basic Res Cardiol. 2014;109:414 pubmed publisher
    ..12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], which is synthesized by arachidonate 12-lipoxygenase (ALOX12). Therefore, we examined whether HPC protects the myocardium against IR via the ALOX12/TRPV1 pathway...

More Information


  1. Ikemoto S, Sugimura K, Kuratukuri K, Nakatani T. Antitumor effects of lipoxygenase inhibitors on murine bladder cancer cell line (MBT-2). Anticancer Res. 2004;24:733-6 pubmed
    ..In an in vivo experiment, the antitumor effects of baicalein administration on C3H/HeN mice implanted with MBT-2 were recognized. These results suggested that LOX inhibition may be significant in the treatment of bladder cancer. ..
  2. 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. ..
  3. Li J, Wang H, Rosenberg P. Vitamin K prevents oxidative cell death by inhibiting activation of 12-lipoxygenase in developing oligodendrocytes. J Neurosci Res. 2009;87:1997-2005 pubmed publisher
    ..In summary, our data indicate that vitamin K prevents oxidative cell death by blocking activation of 12-LOX and ROS generation. ..
  4. Funk C, Furci L, Fitzgerald G. Molecular cloning, primary structure, and expression of the human platelet/erythroleukemia cell 12-lipoxygenase. Proc Natl Acad Sci U S A. 1990;87:5638-42 pubmed
    ..The availability of cDNA probes for human platelet/HEL cell 12-lipoxygenase should facilitate elucidation of the biological role of this pathway. ..
  5. 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
  6. Kong S, Bodyak N, Yue P, Liu Z, Brown J, Izumo S, et al. Genetic expression profiles during physiological and pathological cardiac hypertrophy and heart failure in rats. Physiol Genomics. 2005;21:34-42 pubmed
    ..In addition, there were significant changes in glucose/insulin signaling, protein biosynthesis, and epidermal growth factor signaling during physiological hypertrophy but not during pathological hypertrophy. ..
  7. 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
    ..vehicle-treated and mock-transfected controls. We detected the following primary intrinsic activities: 12-LOX (Alox12, Alox15), 15-LOX (Alox15b), and HXS (Alox12, Alox15)...
  8. Kumar N, Goodchild A, Li Q, Pilowsky P. An aldosterone-related system in the ventrolateral medulla oblongata of spontaneously hypertensive and Wistar-Kyoto rats. Clin Exp Pharmacol Physiol. 2006;33:71-5 pubmed
    ..04). Thus, we have shown for the first time that components of the aldosterone cascade are present in the VLM. Our results suggest that there may be a differential gene expression profile in the brainstem for genetic hypertension. ..
  9. Chen X, Brash A, Funk C. Purification and characterization of recombinant histidine-tagged human platelet 12-lipoxygenase expressed in a baculovirus/insect cell system. Eur J Biochem. 1993;214:845-52 pubmed
    ..The isolation of large quantities of pure human platelet 12-lipoxygenase should facilitate detailed biochemical structure/function studies. ..
  10. Kurusu S, Jinno M, Ehara H, Yonezawa T, Kawaminami M. Inhibition of ovulation by a lipoxygenase inhibitor involves reduced cyclooxygenase-2 expression and prostaglandin E2 production in gonadotropin-primed immature rats. Reproduction. 2009;137:59-66 pubmed publisher
    ..Immunohistochemistry revealed the expression of ALOX5 and ALOX12 in both thecal and granulosa layers of preovulatory follicles and, notably, the augmented immunoreactivities ..
  11. Wang H, Li J, Follett P, Zhang Y, Cotanche D, Jensen F, et al. 12-Lipoxygenase plays a key role in cell death caused by glutathione depletion and arachidonic acid in rat oligodendrocytes. Eur J Neurosci. 2004;20:2049-58 pubmed
    ..These results suggest that 12-LOX activation plays a key role in oxidative stress-induced OL death. ..
  12. Xu H, Wang W, Zhang Y, Cheng Y, Xu Z. Effect of angiotensin II type 1 receptor blocker on 12-lipoxygenase activity and slit diaphragm protein expression in type 2 diabetic rat glomeruli. J Nephrol. 2016;29:775-782 pubmed
    ..ARB potentially ameliorates DN via the up-regulation of glomerular nephrin and P-cadherin expression through the inhibition of 12-LO activation in the glomeruli of rats with DN. ..
  13. Zhang Y, Wang H, Li J, Jimenez D, Levitan E, Aizenman E, et al. Peroxynitrite-induced neuronal apoptosis is mediated by intracellular zinc release and 12-lipoxygenase activation. J Neurosci. 2004;24:10616-27 pubmed
  14. 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. ..
  15. 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. ..
  16. Bogatcheva N, Sergeeva M, Dudek S, Verin A. Arachidonic acid cascade in endothelial pathobiology. Microvasc Res. 2005;69:107-27 pubmed
    ..This review discusses endothelial-specific synthesis and action of arachidonic acid derivatives with a particular focus on the mechanisms of signal transduction and associated intracellular protein targets. ..
  17. Raso E, Dome B, Somlai B, Zacharek A, Hagmann W, Honn K, et al. Molecular identification, localization and function of platelet-type 12-lipoxygenase in human melanoma progression, under experimental and clinical conditions. Melanoma Res. 2004;14:245-50 pubmed
    ..Co-expression of two megakaryocytic genes, p12-LOX and alphaIIb integrin chains, was found to be a frequent phenomenon in human melanoma (approximately 70%) suggesting a common regulatory defect in this tumor. ..
  18. 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...
  19. Johnson E, Brass L, Funk C. Increased platelet sensitivity to ADP in mice lacking platelet-type 12-lipoxygenase. Proc Natl Acad Sci U S A. 1998;95:3100-5 pubmed
    ..The enhanced ADP sensitivity of P-12LO-/- mice appears to reveal a mechanism by which a product of the P-12LO pathway suppresses platelet activation by ADP. ..
  20. 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. ..
  21. 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. ..
  22. Hussain H, Shornick L, Shannon V, Wilson J, Funk C, Pentland A, et al. Epidermis contains platelet-type 12-lipoxygenase that is overexpressed in germinal layer keratinocytes in psoriasis. Am J Physiol. 1994;266:C243-53 pubmed
  23. Matsuyama M, Nakatani T, Hase T, Kawahito Y, Sano H, Kawamura M, et al. The expression of cyclooxygenases and lipoxygenases in renal ischemia-reperfusion injury. Transplant Proc. 2004;36:1939-42 pubmed
    ..Several hours after the maximum of COX-2 and LOXs expressions, the maximal renal I/R injury was observed. These results suggest a relationship between COX-2 and LOXs expressions and renal I/R injury. ..
  24. 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. ..
  25. Guo Q, Miao L, Li B, Ma F, Liu N, Cai L, et al. Role of 12-lipoxygenase in decreasing P-cadherin and increasing angiotensin II type 1 receptor expression according to glomerular size in type 2 diabetic rats. Am J Physiol Endocrinol Metab. 2011;300:E708-16 pubmed publisher
    ..These results suggest that diabetic proteinuria is mediated by the activation of 12-LO pathway that is partially attributed to the decreased glomerular P-cadherin expression. ..
  26. 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. ..
  27. Shannon V, Stenson W, Holtzman M. Induction of epithelial arachidonate 12-lipoxygenase at active sites of inflammatory bowel disease. Am J Physiol. 1993;264:G104-11 pubmed
  28. 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. ..
  29. Pei H, Gu J, Thimmalapura P, Mison A, Nadler J. Activation of the 12-lipoxygenase and signal transducer and activator of transcription pathway during neointima formation in a model of the metabolic syndrome. Am J Physiol Endocrinol Metab. 2006;290:E92-E102 pubmed
    ..These studies suggest both the presence of an exaggerated injury response in the insulin-resistant obese ZR model and that inflammation plays a major role in mediating neointimal growth. ..
  30. 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. ..
  31. Xu Z, Miao L, Cui Y, Jia Y, Yuan H, Wu M. Angiotensin II type 1 receptor expression is increased via 12-lipoxygenase in high glucose-stimulated glomerular cells and type 2 diabetic glomeruli. Nephrol Dial Transplant. 2009;24:1744-52 pubmed publisher
    ..These results indicate that AT1 expression is enhanced, at least in part, by 12-LO in the type 2 diabetic glomeruli, and 12-LO inhibition can ameliorate DN progression through downregulation of AT1 expression. ..
  32. Tanabe M, Radmark O, Watanabe T, Shiose A, Sumimoto H. Cloning of rat p47phox and comparison with human p47phox. DNA Seq. 2005;16:65-8 pubmed
    ..Although rat 12-lipoxygenase interacted with human p47phox in a yeast two-hybrid system, this was not the case for rat p47phox. ..
  33. Yang C, Kurczab T, Down G, Kealey T, Langlands K. Gene expression profiling of the ageing rat vibrissa follicle. Br J Dermatol. 2005;153:22-8 pubmed
    ..8-fold) showed the greatest increases. Decreased expression was found in 19 transcripts, most notably in ALOX12 (13.3-fold) and GAP43 (12.6-fold) expression...
  34. Chen Y, Duniec Z, Liu B, Hagmann W, Gao X, Shimoji K, et al. Endogenous 12(S)-HETE production by tumor cells and its role in metastasis. Cancer Res. 1994;54:1574-9 pubmed
  35. Zeeneldin A, Mohamed A, Abdel H, Taha F, Goda I, Abodeef W. Survival effects of cyclooxygenase-2 and 12-lipooxygenase in Egyptian women with operable breast cancer. Indian J Cancer. 2009;46:54-60 pubmed
    ..COX-2 over-expression was associated with poor prognostic criteria in BC, but did not affect DFS or OS. 12-LOX over-expression was associated with better DFS, but not OS. ..
  36. 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. ..
  37. Yoshimura R, Matsuyama M, Mitsuhashi M, Takemoto Y, Tsuchida K, Kawahito Y, et al. Relationship between lipoxygenase and human testicular cancer. Int J Mol Med. 2004;13:389-93 pubmed
    ..The LOX inhibitors inhibited the growth of TC cells. LOX is induced in TC, and results may suggest that LOXs are essential for cell growth of TC cells. ..
  38. Nie D, Tang K, Diglio C, Honn K. Eicosanoid regulation of angiogenesis: role of endothelial arachidonate 12-lipoxygenase. Blood. 2000;95:2304-11 pubmed
    ..These findings demonstrate that AA metabolism in endothelial cells, especially the 12-LOX pathway, plays a critical role in angiogenesis. ..
  39. Yoshimoto T, Takahashi Y. Arachidonate 12-lipoxygenases. Prostaglandins Other Lipid Mediat. 2002;68-69:245-62 pubmed
    ..There are important roles for the enzymes and their products in several biological systems including those involved in atherosclerosis and neurotransmission. ..
  40. 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)...
  41. 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. ..
  42. Romano M, Chen X, Takahashi Y, Yamamoto S, Funk C, Serhan C. Lipoxin synthase activity of human platelet 12-lipoxygenase. Biochem J. 1993;296 ( Pt 1):127-33 pubmed
    ..These results provide direct evidence for LXA4 and LXB4 synthase activity of human platelet 12-LO. Moreover, they suggest that 12-LO is a dual-function enzyme that carries both oxygenase and lipoxin synthase activity. ..
  43. 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. ..
  44. Tohjima T, Honda N, Mochizuki K, Kinoshita J, Watanabe K, Arisaka T, et al. Decreased activity of arachidonate 12-lipoxygenase in platelets of Japanese patients with non-insulin-dependent diabetes mellitus. Metabolism. 1998;47:257-63 pubmed
    ..These observations suggest that the activity of 12-lipoxygenase in the platelets of patients with NIDDM is decreased by prolonged hyperglycemia. The mechanism involved requires further investigation. ..
  45. Cui Y, Liu N, Ma F, Sun W, Wu H, Xu Z, et al. Role of histone modification in 12?lipoxygenase?associated p21 gene regulation. Mol Med Rep. 2016;14:3978-84 pubmed publisher
    ..Therefore, enhanced H3K9Ac and H3K4Me1 in the p21 promoter and transcription regions, and decreased H3K9Me3 in the p21 promoter increased the expression of p21. ..
  46. 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. ..
  47. 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. ..
  48. Weisinger G, Grafi Cohen M, Hirsh M, Knoll E, Sharon O, Many A, et al. 12S-Lipoxygenase is necessary for human vascular smooth muscle cell survival. Exp Cell Res. 2013;319:1586-93 pubmed publisher
    ..Hence, biochemical 12LO inhibition or 12LO-antisense knockdown in VSMC can induce programmed cell death. These observations suggest a previously unrecognized association between human VSMC survivability and 12LO. ..
  49. Izumi T, Hoshiko S, Radmark O, Samuelsson B. Cloning of the cDNA for human 12-lipoxygenase. Proc Natl Acad Sci U S A. 1990;87:7477-81 pubmed
    ..Human platelet 12-lipoxygenase has been difficult to purify to homogeneity. The cloning of this cDNA will increase the possibilities to elucidate the structure and function of this enzyme. ..