ALOX5

Summary

Gene Symbol: ALOX5
Description: arachidonate 5-lipoxygenase
Alias: 5-LO, 5-LOX, 5LPG, LOG5, arachidonate 5-lipoxygenase, LOX-5, arachidonic 5-lipoxygenase alpha-10 isoform, arachidonic 5-lipoxygenase delta-10-13 isoform, arachidonic 5-lipoxygenase delta-13 isoform, arachidonic 5-lipoxygenase delta-p10 isoform, arachidonic acid 5-lipoxygenase, leukotriene A4 synthase
Species: human
Products:     ALOX5

Top Publications

  1. Jakobsson P, Shaskin P, Larsson P, Feltenmark S, Odlander B, Aguilar Santelises M, et al. Studies on the regulation and localization of 5-lipoxygenase in human B-lymphocytes. Eur J Biochem. 1995;232:37-46 pubmed
    ..In contrast, neither human peripheral T-lymphocytes nor Jurkat cells were stained. These results suggest that 5-lipoxygenase and its products function in the nucleus of B-lymphocytes. ..
  2. Dwyer J, Allayee H, Dwyer K, Fan J, Wu H, Mar R, et al. Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis. N Engl J Med. 2004;350:29-37 pubmed
    ..The observed diet-gene interactions further suggest that dietary n-6 polyunsaturated fatty acids promote, whereas marine n-3 fatty acids inhibit, leukotriene-mediated inflammation that leads to atherosclerosis in this subpopulation. ..
  3. Qiu H, Gabrielsen A, Agardh H, Wan M, Wetterholm A, Wong C, et al. Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability. Proc Natl Acad Sci U S A. 2006;103:8161-6 pubmed
    ..The abundant expression of LTA4H and correlation with plaque instability identify LTA4H as a potential target for pharmacological intervention in treatment of human atherosclerosis. ..
  4. Rakonjac M, Fischer L, Provost P, Werz O, Steinhilber D, Samuelsson B, et al. Coactosin-like protein supports 5-lipoxygenase enzyme activity and up-regulates leukotriene A4 production. Proc Natl Acad Sci U S A. 2006;103:13150-5 pubmed
    ..Furthermore, in stimulated cells, CLP appears to function in a complex together with 5LO and membranes, increasing the capacity of 5LO for leukotriene biosynthesis. ..
  5. Woods J, Evans J, Ethier D, Scott S, Vickers P, Hearn L, et al. 5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes. J Exp Med. 1993;178:1935-46 pubmed
  6. Cipollone F, Mezzetti A, Fazia M, Cuccurullo C, Iezzi A, Ucchino S, et al. Association between 5-lipoxygenase expression and plaque instability in humans. Arterioscler Thromb Vasc Biol. 2005;25:1665-70 pubmed
    ..0001). The expression of 5-LO is elevated in symptomatic compared with asymptomatic plaques and is associated with acute ischemic syndromes, possibly through the generation of LTB4, subsequent MMP biosynthesis, and plaque rupture. ..
  7. Choi J, Park H, Oh H, Lee J, Suh Y, Park C, et al. Leukotriene-related gene polymorphisms in ASA-intolerant asthma: an association with a haplotype of 5-lipoxygenase. Hum Genet. 2004;114:337-44 pubmed
    ..The single-base extension method was used to genotype SNPs in 5-lipoxygenase (ALOX5, -1708G-->A, 21C-->T, 270G-->A, 1728G-->A), ALOX5-activating protein (ALOX5AP, 218A-->G), ..
  8. Wang Q, Zhang W, Liu Q, Zhang X, Lv N, Ye L, et al. A mutant of hepatitis B virus X protein (HBxDelta127) promotes cell growth through a positive feedback loop involving 5-lipoxygenase and fatty acid synthase. Neoplasia. 2010;12:103-15 pubmed
    ..Thus, our finding provides a new insight into the mechanism involving the promotion of cell growth mediated by HBxDelta127. ..
  9. Sayers I, Barton S, Rorke S, Sawyer J, Peng Q, Beghe B, et al. Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population. Clin Exp Allergy. 2003;33:1103-10 pubmed
    ..within the FLAP (ALOX5AP) gene promoter and test the role of these and the previously identified 5-LO (ALOX5) Sp1 promoter polymorphism in asthma susceptibility...

More Information

Publications99

  1. Zhou Y, Wang J, Li L, Yang H, Wen D, He Q. Expanding expression of the 5-lipoxygenase/leukotriene B4 pathway in atherosclerotic lesions of diabetic patients promotes plaque instability. Biochem Biophys Res Commun. 2007;363:30-6 pubmed
    ..Hence, anti-LTs may be useful, not only in reducing atherogenesis, but also in the prevention and treatment of acute atherothrombotic events in diabetic patients. ..
  2. Allayee H, Baylin A, Hartiala J, Wijesuriya H, Mehrabian M, Lusis A, et al. Nutrigenetic association of the 5-lipoxygenase gene with myocardial infarction. Am J Clin Nutr. 2008;88:934-40 pubmed
    ..0001). The 3 and 4 variants lead to higher 5-LO expression and provide additional evidence that these alleles are associated with greater risks of atherosclerosis and MI in the context of a high-AA diet. ..
  3. Werz O, Tretiakova I, Michel A, Ulke Lemee A, Hörnig M, Franke L, et al. Caspase-mediated degradation of human 5-lipoxygenase in B lymphocytic cells. Proc Natl Acad Sci U S A. 2005;102:13164-9 pubmed
    ..We suggest that splitting of BL41-E95-A cells induces de novo synthesis of a protein involved in the activation of casp-6, which cleaves 5-LO. ..
  4. Mahshid Y, Lisy M, Wang X, Spanbroek R, Flygare J, Christensson B, et al. High expression of 5-lipoxygenase in normal and malignant mantle zone B lymphocytes. BMC Immunol. 2009;10:2 pubmed publisher
  5. 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. ..
  6. 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. ..
  7. Gheorghe K, Korotkova M, Catrina A, Backman L, af Klint E, Claesson H, et al. Expression of 5-lipoxygenase and 15-lipoxygenase in rheumatoid arthritis synovium and effects of intraarticular glucocorticoids. Arthritis Res Ther. 2009;11:R83 pubmed publisher
    ..These data demonstrate that local therapy with GC decreases 5-LO expression in RA synovium and offer an additional possible mechanism for the efficiency of intraarticular adjuvant therapy in RA. ..
  8. Boudreau L, Bertin J, Robichaud P, Laflamme M, Ouellette R, Flamand N, et al. Novel 5-lipoxygenase isoforms affect the biosynthesis of 5-lipoxygenase products. FASEB J. 2011;25:1097-105 pubmed publisher
    ..These alternative 5-LO isoforms may represent a new mechanism for the regulation of the 5-LO pathway and lipid mediator biosynthesis. ..
  9. Wright L, Tuder R, Wang J, Cool C, Lepley R, Voelkel N. 5-Lipoxygenase and 5-lipoxygenase activating protein (FLAP) immunoreactivity in lungs from patients with primary pulmonary hypertension. Am J Respir Crit Care Med. 1998;157:219-29 pubmed
  10. Brock T, McNish R, Bailie M, Peters Golden M. Rapid import of cytosolic 5-lipoxygenase into the nucleus of neutrophils after in vivo recruitment and in vitro adherence. J Biol Chem. 1997;272:8276-80 pubmed
    ..Nuclear import of 5-lipoxygenase may be a universal accompaniment of neutrophil recruitment into sites of inflammation, and this may be associated with alterations in enzymatic function. ..
  11. Dixon R, Jones R, Diehl R, Bennett C, Kargman S, Rouzer C. Cloning of the cDNA for human 5-lipoxygenase. Proc Natl Acad Sci U S A. 1988;85:416-20 pubmed
    ..Thus, 5-LO appears to be a member of a larger family of related enzymes. ..
  12. Soumaoro L, Iida S, Uetake H, Ishiguro M, Takagi Y, Higuchi T, et al. Expression of 5-lipoxygenase in human colorectal cancer. World J Gastroenterol. 2006;12:6355-60 pubmed
    ..392, P = 0.0002), depth or vessel invasion. These results suggest that 5-Lox is up-regulated in colorectal cancer and that inhibition of its expression might be valuable in the prevention and treatment of colorectal cancer. ..
  13. Hennig R, Ding X, Tong W, Schneider M, Standop J, Friess H, et al. 5-Lipoxygenase and leukotriene B(4) receptor are expressed in human pancreatic cancers but not in pancreatic ducts in normal tissue. Am J Pathol. 2002;161:421-8 pubmed
    ..These findings provide further evidence of up-regulation of this pathway in pancreatic cancer and that LOX inhibitors are likely to be valuable in the treatment of this dreadful disease. ..
  14. Spanbroek R, Stark H, Janssen Timmen U, Kraft S, Hildner M, Andl T, et al. 5-Lipoxygenase expression in Langerhans cells of normal human epidermis. Proc Natl Acad Sci U S A. 1998;95:663-8 pubmed
    ..These data show that naive LCs are major, and possibly the sole, 5-LO pathway expressing cells in the normal human epidermis. ..
  15. Lee S, Choi E, Seo K, Bae J, Kim Y, Park S, et al. 5-Lipoxygenase plays a pivotal role in endothelial adhesion of monocytes via an increased expression of Mac-1. Cardiovasc Res. 2013;99:724-33 pubmed publisher
  16. Melstrom L, Bentrem D, Salabat M, Kennedy T, Ding X, Strouch M, et al. Overexpression of 5-lipoxygenase in colon polyps and cancer and the effect of 5-LOX inhibitors in vitro and in a murine model. Clin Cancer Res. 2008;14:6525-30 pubmed publisher
    ..The blockade of 5-LOX inhibits colon cancer cell proliferation both in vitro and in vivo and may prove a beneficial chemopreventive therapy in colon cancer. ..
  17. Janssen Timmen U, Vickers P, Wittig U, Lehmann W, Stark H, Fusenig N, et al. Expression of 5-lipoxygenase in differentiating human skin keratinocytes. Proc Natl Acad Sci U S A. 1995;92:6966-70 pubmed
    ..These results show that 5-LO gene expression is an intrinsic property of human skin keratinocytes. ..
  18. Schnur N, Seuter S, Katryniok C, Radmark O, Steinhilber D. The histone deacetylase inhibitor trichostatin A mediates upregulation of 5-lipoxygenase promoter activity by recruitment of Sp1 to distinct GC-boxes. Biochim Biophys Acta. 2007;1771:1271-82 pubmed
    ..This is the first report demonstrating that Sp3 is involved in the regulation of 5-LO promoter activity. In summary, we show that TsA increases 5-LO promoter activity by the enhanced recruitment of Sp1 and Sp3 to the 5-LO promoter. ..
  19. Seuter S, Sorg B, Steinhilber D. The coding sequence mediates induction of 5-lipoxygenase expression by Smads3/4. Biochem Biophys Res Commun. 2006;348:1403-10 pubmed
    ..Sequence analysis and deletion studies indicate the existence of up to four Smad binding elements and at least one TGFbeta responsive element far downstream of the transcriptional start site. ..
  20. Elias I, Ferre T, Vilà L, Munoz S, Casellas A, Garcia M, et al. ALOX5AP Overexpression in Adipose Tissue Leads to LXA4 Production and Protection Against Diet-Induced Obesity and Insulin Resistance. Diabetes. 2016;65:2139-50 pubmed publisher
    ..Both lipid mediators derive from the same pathway, in which arachidonate 5-lipoxygenase (ALOX5) and its partner, arachidonate 5-lipoxygenase-activating protein (ALOX5AP), are involved...
  21. Wculek S, Malanchi I. Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature. 2015;528:413-7 pubmed publisher
    ..Genetic or pharmacological inhibition of the leukotriene-generating enzyme arachidonate 5-lipoxygenase (Alox5) abrogates neutrophil pro-metastatic activity and consequently reduces metastasis...
  22. Kennedy B, Harris R. Cyclooxygenase and lipoxygenase gene expression in the inflammogenesis of breast cancer. Inflammopharmacology. 2018;: pubmed publisher
    ..the expression of major inflammatory genes, cyclooxygenase-1 and 2 (COX1, COX2) and arachidonate 5-lipoxygenase (ALOX5) in 1090 tumor samples of invasive breast cancer from The Cancer Genome Atlas (TCGA)...
  23. Menkhorst E, Van Sinderen M, Rainczuk K, Cuman C, Winship A, Dimitriadis E. Invasive trophoblast promote stromal fibroblast decidualization via Profilin 1 and ALOX5. Sci Rep. 2017;7:8690 pubmed publisher
    ..PFN1 down-regulated the expression of lipoxygenase arachidonate 5-lipoxygenase (ALOX5) in HESC and THP-1 macrophages...
  24. Bäck M. Inhibitors of the 5-lipoxygenase pathway in atherosclerosis. Curr Pharm Des. 2009;15:3116-32 pubmed
    ..The present review summarizes the components of this pathway; the enzymes 5-lipoxygenase (5-LO, ALOX5) with its activating protein, FLAP (ALOX5AP), LTA(4) hydrolase and LTC(4) synthase, as well as the receptors for ..
  25. Hoshiko S, Radmark O, Samuelsson B. Characterization of the human 5-lipoxygenase gene promoter. Proc Natl Acad Sci U S A. 1990;87:9073-7 pubmed
    ..Furthermore, HL-60 nuclear extracts contained specific nuclear factor(s) binding to 5-lipoxygenase promoter DNA, which could not be detected in HeLa cell nuclear extracts. ..
  26. Knab L, Schultz M, Principe D, Mascarinas W, Gounaris E, Munshi H, et al. Ablation of 5-lipoxygenase mitigates pancreatic lesion development. J Surg Res. 2015;194:481-7 pubmed publisher
  27. Tran H, Marton M, Herz C, Maul R, Baldermann S, Schreiner M, et al. Nasturtium (Indian cress, Tropaeolum majus nanum) dually blocks the COX and LOX pathway in primary human immune cells. Phytomedicine. 2016;23:611-20 pubmed publisher
    ..This study provides a rationale for the anti-inflammatory efficacy of nasturtium observed in man and gives first insight into the underlying molecular mechanisms. ..
  28. van der Laan S, Foroughi Asl H, van den Borne P, van Setten J, van der Perk M, Van de Weg S, et al. Variants in ALOX5, ALOX5AP and LTA4H are not associated with atherosclerotic plaque phenotypes: the Athero-Express Genomics Study. Atherosclerosis. 2015;239:528-38 pubmed publisher
    The eicosanoid genes ALOX5, ALOX5AP and LTA4H have been implicated in atherosclerosis. We assessed the impact of common variants in these genes on gene expression, circulating protein levels, and atherosclerotic plaque phenotypes...
  29. Provost P, Samuelsson B, Radmark O. Interaction of 5-lipoxygenase with cellular proteins. Proc Natl Acad Sci U S A. 1999;96:1881-5 pubmed
    ..The identification of these 5LO-interacting proteins provides additional approaches to studies of the cellular functions of 5LO. ..
  30. Kapral M, Wawszczyk J, Sośnicki S, Jesse K, Węglarz L. Modulating effect of inositol hexaphosphate on arachidonic acid-dependent pathways in colon cancer cells. Prostaglandins Other Lipid Mediat. 2017;131:41-48 pubmed publisher
  31. Chang J, Tang N, Fang Q, Zhu K, Liu L, Xiong X, et al. TEMPORARY REMOVAL: Inhibition of COX-2 and 5-LOX regulates the progression of colorectal cancer by promoting PTEN and suppressing PI3K/AKT pathway. Biochem Biophys Res Commun. 2018;: pubmed publisher
    ..The full Elsevier Policy on Article Withdrawal can be found athttps://www.elsevier.com/about/our-business/policies/article-withdrawal. ..
  32. Capó X, Martorell M, Sureda A, Tur J, Pons A. Effects of dietary Docosahexaenoic, training and acute exercise on lipid mediators. J Int Soc Sports Nutr. 2016;13:16 pubmed publisher
    ..Exercise primed PBMCs to enhance PGE1, PGE2 and RvD1 production in response to LPS. The project was registered at ClinicalTrial.gov (NCT02177383). ..
  33. Kuchárová B, Mikeš J, Jendželovský R, Vargová J, Mikešová L, Jendželovská Z, et al. Potentiation of hypericin-mediated photodynamic therapy cytotoxicity by MK-886: focus on ABC transporters, GDF-15 and redox status. Photodiagnosis Photodyn Ther. 2015;12:490-503 pubmed publisher
    ..However, complex cellular response to MK-886 pretreatment needs to be considered and further elucidated. ..
  34. Studýnková J, Kuchen S, Jeisy E, Schedel J, Charvat F, Jarosova K, et al. The expression of cyclooxygenase-1, cyclooxygenase-2 and 5-lipoxygenase in inflammatory muscle tissue of patients with polymyositis and dermatomyositis. Clin Exp Rheumatol. 2004;22:395-402 pubmed
    ..This expression was increased in affected tissues detected by MRI, which may suggest a role of COX-1, COX-2, and 5-LOX in the pathogenesis of IIM. ..
  35. White K, Schildkraut J, Palmieri R, Iversen E, Berchuck A, Vierkant R, et al. Ovarian cancer risk associated with inherited inflammation-related variants. Cancer Res. 2012;72:1064-9 pubmed publisher
    ..Genotype at rs1864414 in the arachidonate 5-lipoxygenase ALOX5 was also associated with decreased risk...
  36. Chatterjee A, Komshian S, Sansbury B, Wu B, Mottola G, Chen M, et al. Biosynthesis of proresolving lipid mediators by vascular cells and tissues. FASEB J. 2017;31:3393-3402 pubmed publisher
    ..Chatterjee, A., Komshian, S., Sansbury, B. E., Wu, B., Mottola, G., Chen, M., Spite, M., Conte, M. S. Biosynthesis of proresolving lipid mediators by vascular cells and tissues. ..
  37. Liao D, Qian B, Zhang Y, Wu K, Xu M. Inhibition of 5-lipoxygenase represses neutrophils activation and activates apoptosis in pancreatic tissues during acute necrotizing pancreatitis. Biochem Biophys Res Commun. 2018;498:79-85 pubmed publisher
    ..Our results show that 5-LOX plays an important role in activating apoptosis and repressing neutrophils activation during ANP. The current study suggests that 5-LOX can be used as a potential target for the treatment of ANP. ..
  38. Dincbas Renqvist V, Pépin G, Rakonjac M, Plante I, Ouellet D, Hermansson A, et al. Human Dicer C-terminus functions as a 5-lipoxygenase binding domain. Biochim Biophys Acta. 2009;1789:99-108 pubmed publisher
    ..Providing a link between miRNA-mediated regulation of gene expression and inflammation, our results suggest that the formation of miRNAs may be regulated by 5LO in leukocytes and cancer cells expressing this lipoxygenase. ..
  39. Foroud T, Ichikawa S, Koller D, Lai D, Curry L, Xuei X, et al. Association studies of ALOX5 and bone mineral density in healthy adults. Osteoporos Int. 2008;19:637-43 pubmed
    Animal studies suggest that arachidonate 5-lipoxygenase (encoded by ALOX5) may be a genetic determinant of bone mineral density...
  40. Schentrup A, Allayee H, Lima J, Johnson J, Langaee T. Genotyping the GGGCGG tandem repeat promoter polymorphism in the 5-lipoxygenase enzyme gene (ALOX5) by pyrosequencing assay. Genet Test Mol Biomarkers. 2009;13:361-5 pubmed publisher
    ..In particular, a short tandem repeat polymorphism [GGCGGG] in the promoter region of ALOX5 has been implicated as an important marker for inflammatory diseases...
  41. Koeberle A, Zettl H, Greiner C, Wurglics M, Schubert Zsilavecz M, Werz O. Pirinixic acid derivatives as novel dual inhibitors of microsomal prostaglandin E2 synthase-1 and 5-lipoxygenase. J Med Chem. 2008;51:8068-76 pubmed publisher
    ..Taken together, these pirinixic acid derivatives constitute a novel class of dual mPGES-1/5-LO inhibitors with a promising pharmacological profile and a potential for therapeutic use. ..
  42. Kuhn H, Anton M, Gerth C, Habenicht A. Amino acid differences in the deduced 5-lipoxygenase sequence of CAST atherosclerosis-resistance mice confer impaired activity when introduced into the human ortholog. Arterioscler Thromb Vasc Biol. 2003;23:1072-6 pubmed
  43. Prado M, Locachevic G, Zoccal K, Paula Silva F, Fontanari C, Ferreira J, et al. Leukotriene B4 is essential for lung host defence and alpha-defensin-1 production during Achromobacter xylosoxidans infection. Sci Rep. 2017;7:17658 pubmed publisher
    ..Wild-type (129sv) and LTB4 deficient (Alox5 -/-) mice were intratracheally infected with A. xylosoxidans...
  44. Luo Y, Xu M, Gao W, Tao K. [Knockdown of Alox5 gene promotes apoptosis of K562/ADM cells]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017;33:1398-1403 pubmed
    Objective To investigate the effect of short hairpin RNA (shRNA) knockdown of arachidonate 5-lipoxygenase (Alox5) gene on the apoptosis of resistant chronic myeloid leukemia K562/ADM cells...
  45. Kim S, Ye Y, Hur G, Lee S, Sampson A, Lee H, et al. CysLTR1 promoter polymorphism and requirement for leukotriene receptor antagonist in aspirin-intolerant asthma patients. Pharmacogenomics. 2007;8:1143-50 pubmed
    ..This study evaluated associations between the clinical requirement for LTRA and genetic polymorphisms of the ALOX5, LTC4S, COX-2, CysLTR1 and TBXA2R genes in the arachidonic acid cascade in the long-term management of 89 AIA ..
  46. Cabral M, Martín Venegas R, Moreno J. Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2 synthesis. Physiol Rep. 2015;3: pubmed publisher
    ..These findings will help facilitate our understanding of how inflammatory mediators can affect the survival and dissemination of intestinal carcinoma cells. ..
  47. Lim J, Goh F, Sagineedu S, Yong A, Sidik S, Lajis N, et al. A semisynthetic diterpenoid lactone inhibits NF-?B signalling to ameliorate inflammation and airway hyperresponsiveness in a mouse asthma model. Toxicol Appl Pharmacol. 2016;302:10-22 pubmed publisher
    ..SRS27 is the first known DDAG analogue effective in ameliorating inflammation and airway hyperresponsiveness in the ovalbumin-induced mouse asthma model. ..
  48. Ochs M, Sorg B, Pufahl L, Grez M, Suess B, Steinhilber D. Post-transcriptional regulation of 5-lipoxygenase mRNA expression via alternative splicing and nonsense-mediated mRNA decay. PLoS ONE. 2012;7:e31363 pubmed publisher
    ..In contrast, the mature 5-LO mRNA transcript was not affected by UPF knockdown. Thus, the data suggest that the coupling of alternative splicing and NMD is involved in the regulation of 5-LO gene expression. ..
  49. Ayuso P, Plaza Serón M, Blanca López N, Doña I, Campo P, Canto G, et al. Genetic variants in arachidonic acid pathway genes associated with NSAID-exacerbated respiratory disease. Pharmacogenomics. 2015;16:825-39 pubmed publisher
    ..0009, pc = 0.0091; NERD vs controls; p = 0.0064, pc = 0.045). Differences in ALOX5 copy number variations were also found (NERD vs NTA; p = 0.010; NERD vs controls; p = 0.0001)...
  50. Gammelmark A, Nielsen M, Lundbye Christensen S, Tjønneland A, Schmidt E, Overvad K. Common Polymorphisms in the 5-Lipoxygenase Pathway and Risk of Incident Myocardial Infarction: A Danish Case-Cohort Study. PLoS ONE. 2016;11:e0167217 pubmed publisher
    ..In conclusion, some common polymorphisms in the 5-lipoxygenase pathway were modestly associated with incident MI, suggesting a potential role for this pathway in the development of cardiovascular disease. ..
  51. Mancini J, Li C, Vickers P. 5-Lipoxygenase activity in the human pancreas. J Lipid Mediat. 1993;8:145-50 pubmed
    ..Western blot analysis demonstrated that the human pancreas contains low levels of 5-lipoxygenase-activating protein (FLAP) in addition to 5-LO. ..
  52. Pallio G, Bitto A, Pizzino G, Galfo F, Irrera N, Minutoli L, et al. Use of a balanced dual cyclooxygenase-1/2 and 5-lypoxygenase inhibitor in experimental colitis. Eur J Pharmacol. 2016;789:152-162 pubmed publisher
    ..Our results show that flavocoxid has protective effect in IBDs and may represents a future safe treatment for inflammatory bowel diseases. ..
  53. Joshi V, Venkatesha S, Ramakrishnan C, Nanjaraj Urs A, Hiremath V, Moudgil K, et al. Celastrol modulates inflammation through inhibition of the catalytic activity of mediators of arachidonic acid pathway: Secretory phospholipase A2 group IIA, 5-lipoxygenase and cyclooxygenase-2. Pharmacol Res. 2016;113:265-275 pubmed publisher
    ..Thus, celastrol modulates inflammatory responses by targeting multiple enzymes of AA pathway. ..
  54. Tantisira K, Lima J, Sylvia J, Klanderman B, Weiss S. 5-lipoxygenase pharmacogenetics in asthma: overlap with Cys-leukotriene receptor antagonist loci. Pharmacogenet Genomics. 2009;19:244-7 pubmed publisher
    ..that had previously been interrogated for association with montelukast response in five candidate genes (ABCC1, ALOX5, CYSLTR1, LTA4H, LTC4S) in a population of 577 asthmatics who participated in a clinical trial comparing ..
  55. Devi N, Ramanan M, Paragi Vedanthi P, Doble M. Phytochemicals as multi-target inhibitors of the inflammatory pathway- A modeling and experimental study. Biochem Biophys Res Commun. 2017;484:467-473 pubmed publisher
    ..2 and 72.0% and ferulic acid by 74.3 and 54.4% respectively. This approach offers a promising theoretical combined with experimental strategy for designing novel molecules against inflammatory enzymes. ..
  56. Zhou G, Ding X, Huang J, Zhang H, Wu S. Suppression of 5-lipoxygenase gene is involved in triptolide-induced apoptosis in pancreatic tumor cell lines. Biochim Biophys Acta. 2007;1770:1021-7 pubmed
    ..We also provide evidence that TL has clinical therapeutic value for patients with pancreatic cancer. ..
  57. Wang J, John E, Ingles S. 5-lipoxygenase and 5-lipoxygenase-activating protein gene polymorphisms, dietary linoleic acid, and risk for breast cancer. Cancer Epidemiol Biomarkers Prev. 2008;17:2748-54 pubmed publisher
    ..and White women from the San Francisco Bay area to examine the association of the 5-lipoxygenase gene (ALOX5) and 5-lipoxygenase-activating protein gene (ALOX5AP) with breast cancer risk...
  58. Gerstmeier J, Weinigel C, Rummler S, RÃ¥dmark O, Werz O, Garscha U. Time-resolved in situ assembly of the leukotriene-synthetic 5-lipoxygenase/5-lipoxygenase-activating protein complex in blood leukocytes. FASEB J. 2016;30:276-85 pubmed publisher
    ..We conclude that FLAP may regulate 5-LO activity in 2 ways: first by inducing an initial flexible association for efficient 5-LO product synthesis, followed by the formation of a tight 5-LO/FLAP complex that terminates 5-LO activity. ..
  59. Brogliato A, Moor A, Kesl S, Guilherme R, Georgii J, Peters Golden M, et al. Critical role of 5-lipoxygenase and heme oxygenase-1 in wound healing. J Invest Dermatol. 2014;134:1436-1445 pubmed publisher
    ..Taken together, our results show that 5-LO disruption improves wound healing and alters fibroblast function by an antioxidant mechanism based on HO-1 induction. Overexpression of HO-1 in wounds may facilitate early wound resolution. ..
  60. Bishayee K, Khuda Bukhsh A. 5-lipoxygenase antagonist therapy: a new approach towards targeted cancer chemotherapy. Acta Biochim Biophys Sin (Shanghai). 2013;45:709-19 pubmed publisher
    ..Studies of these well-characterized agents are therefore warranted for their use as possible candidates for chemotherapeutic studies against the killer disease cancer. ..
  61. Holm J, Grygorczyk R, Lambert I. Volume-sensitive release of organic osmolytes in the human lung epithelial cell line A549: role of the 5-lipoxygenase. Am J Physiol Cell Physiol. 2013;305:C48-60 pubmed publisher
  62. Sorgi C, Zarini S, Martin S, Sanchez R, Scandiuzzi R, Gijón M, et al. Dormant 5-lipoxygenase in inflammatory macrophages is triggered by exogenous arachidonic acid. Sci Rep. 2017;7:10981 pubmed publisher
    ..Although Alox5 expression and the presence of 5-lipoxygenase (5-LO) protein in BMDMs was observed, the absence of leukotrienes ..
  63. Sud ina G, Pushkareva M, Shephard P, Klein T. Cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) selectivity of COX inhibitors. Prostaglandins Leukot Essent Fatty Acids. 2008;78:99-108 pubmed publisher
    ..Surprisingly, ML-3000 had no effect on 5-LOX product synthesis in whole-blood assay. In addition, we could show that inhibition of COX pathways did not increase the transformation of arachidonic acid by the 5-LOX pathway. ..
  64. Butovich I, Lukyanova S, Bachmann C. Dihydroxydocosahexaenoic acids of the neuroprotectin D family: synthesis, structure, and inhibition of human 5-lipoxygenase. J Lipid Res. 2006;47:2462-74 pubmed
    ..These findings suggest that 7,17(S)-diHDHA along with its 10,17(S) counterpart might have anti-inflammatory and anticancer activities, which could be exerted, at least in part, through direct inhibition of 5LOX and 15LOX. ..
  65. Maccarrone M, Navarra M, Catani V, Corasaniti M, Bagetta G, Finazzi Agrò A. Cholesterol-dependent modulation of the toxicity of HIV-1 coat protein gp120 in human neuroblastoma cells. J Neurochem. 2002;82:1444-52 pubmed
    ..Taken together, these results suggest that membrane fluidity may control the neurotoxic effects of HIV-1 glycoprotein gp120. ..
  66. Wang Q, Zhang W, Ye L, Zhang X. A mutant of HBx (HBxDelta127) promotes hepatoma cell growth via sterol regulatory element binding protein 1c involving 5-lipoxygenase. Acta Pharmacol Sin. 2010;31:367-74 pubmed publisher
    ..HBxDelta127 promotes hepatoma cell growth through activating SREBP-1c involving 5-LOX. ..
  67. Šerý O, Hlinecká L, Povová J, Bonczek O, Zeman T, Janout V, et al. Arachidonate 5-lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index. J Neurol Sci. 2016;362:27-32 pubmed publisher
    ..Using a case-control genetic approach, we have identified a SNP (rs10507391) in ALOX5 gene, previously associated with an increased risk of stroke, as a novel genetic risk factor for AD...
  68. Jin T, Xun X, Shi X, Yuan D, Feng T, Geng T, et al. Genetic polymorphisms in very important pharmacogenomic (VIP) variants in the Tibetan population. Genet Mol Res. 2015;14:12497-504 pubmed publisher
    ..05/(82*10)]. rs2115819, rs9934438, and rs689466, located in the ALOX5 (arachidonate 5-lipoxygenase), VKORC1 (vitamin K epoxide reductase complex, subunit 1) and PTGS2 (prostaglandin-..
  69. Che X, Chen C, Ye X, Weng G, Guo X, Yu W, et al. Dual inhibition of COX-2/5-LOX blocks colon cancer proliferation, migration and invasion in vitro. Oncol Rep. 2016;35:1680-8 pubmed publisher
    ..In summary, our data suggest that the inhibition of both COX-2/5-LOX may be an effective therapeutic approach for colon cancer management, particularly for those patients with high expression of COX-2/5-LOX. ..
  70. Shen C, Wu X, Wang B, Sun L, Jiao W, Wang J, et al. ALOX5 is associated with tuberculosis in a subset of the pediatric population of North China. Genet Test Mol Biomarkers. 2013;17:284-8 pubmed publisher
    Genetic factors are involved in the etiology of Mycobacterium tuberculosis infection. Recently, ALOX5 has been identified as a candidate gene for tuberculosis (TB) susceptibility...
  71. Rouzer C, Kargman S. Translocation of 5-lipoxygenase to the membrane in human leukocytes challenged with ionophore A23187. J Biol Chem. 1988;263:10980-8 pubmed
    ..Thus, membrane translocation of 5-lipoxygenase may be an important initial step in the chain of events leading to full activation of this enzyme in the intact leukocyte. ..
  72. Du L, Zhang Z, Luo X, Chen K, Shen X, Jiang H. Binding investigation of human 5-lipoxygenase with its inhibitors by SPR technology correlating with molecular docking simulation. J Biochem. 2006;139:715-23 pubmed
    ..This current work has potential for application in structure-based 5-LOX inhibitor discovery. ..
  73. 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. ..
  74. Joy M, Chakraborty K. Biogenic antioxidative and anti-inflammatory aryl polyketides from the venerid bivalve clam Paphia malabarica. Food Chem. 2017;237:169-180 pubmed publisher
    ..The potential of hitherto undescribed polyketides from P. malabarica as natural antioxidative and anti-inflammatory functional food ingredients was demonstrated in the present study. ..
  75. Shen F, Wang Z, Wu S, Ren S, Man R, Wang B, et al. Synthesis of novel hybrids of pyrazole and coumarin as dual inhibitors of COX-2 and 5-LOX. Bioorg Med Chem Lett. 2017;27:3653-3660 pubmed publisher
    ..Our study might contribute to COX-2, 5-LOX dual inhibitors thus exploit promising novel cancer prevention agents. ..
  76. Subramanian P, Mendez E, Becerra S. A Novel Inhibitor of 5-Lipoxygenase (5-LOX) Prevents Oxidative Stress-Induced Cell Death of Retinal Pigment Epithelium (RPE) Cells. Invest Ophthalmol Vis Sci. 2016;57:4581-8 pubmed publisher
    ..Reverse transcription-PCR of ALOX5 and PNPLA2 genes was performed. Cell viability and death rates were determined using respective biomarkers...
  77. Srivastava P, Vyas V, Variya B, Patel P, Qureshi G, Ghate M. Synthesis, anti-inflammatory, analgesic, 5-lipoxygenase (5-LOX) inhibition activities, and molecular docking study of 7-substituted coumarin derivatives. Bioorg Chem. 2016;67:130-8 pubmed publisher
    ..Presence of OCH3 group in 35 and Cl in 33 at C6-position of benzothiazole ring were found very important substitutions for potent activity. ..
  78. Huang Y, Tan Q, Wu Y, Zhu H, Xiong M, Hu J. RNA Interference Protects Against 5-Lipoxygenase-Induced Cocarcinogen, Benzidine, Oxidation and Cytotoxicity in Human Tracheobronchial Epithelial Cells. Int J Toxicol. 2014;33:297-306 pubmed
    ..This study aimed to determine whether BZD could be activated by arachidonate 5-lipoxygenase (ALOX5) in the human tracheobronchial epithelial cells (HBECs) using RNA interference strategy and a 5-LOX-specific ..
  79. Nagy E, Bäck M. Epigenetic regulation of 5-lipoxygenase in the phenotypic plasticity of valvular interstitial cells associated with aortic valve stenosis. FEBS Lett. 2012;586:1325-9 pubmed publisher
    ..These findings provide a first piece of evidence for epigenetic modifications of VICs in valvular heart disease. ..
  80. Nielsen M, Grønholdt M, Vyberg M, Overvad K, Andreasen A, Due K, et al. Adipose tissue arachidonic acid content is associated with the expression of 5-lipoxygenase in atherosclerotic plaques. Lipids Health Dis. 2013;12:7 pubmed publisher
    ..This association might represent a causal link between adipose tissue arachidonic acid and the risk of myocardial infarction but confirmatory studies are needed. ..
  81. 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. ..
  82. Carlson C, Heagerty P, Nord A, Pritchard D, Ranchalis J, Boguch J, et al. TagSNP evaluation for the association of 42 inflammation loci and vascular disease: evidence of IL6, FGB, ALOX5, NFKBIA, and IL4R loci effects. Hum Genet. 2007;121:65-75 pubmed
    ..We confirm the association of IL6(-174), FGB (-455), and ALOX5 with CAAD and show that multiple ALOX5 SNPs independently predict CAAD...
  83. Ghosh J. Inhibition of arachidonate 5-lipoxygenase triggers prostate cancer cell death through rapid activation of c-Jun N-terminal kinase. Biochem Biophys Res Commun. 2003;307:342-9 pubmed
    ..These findings suggest that the metabolites of arachidonate 5-lipoxygenase promote survival of prostate cancer cells involving down-regulation of stress-activated protein kinase. ..
  84. Chu J, Li J, Hoffman N, Stough A, Madesh M, Praticò D. Regulation of gamma-secretase activating protein by the 5Lipoxygenase: in vitro and in vivo evidence. Sci Rep. 2015;5:11086 pubmed publisher
    ..Taken together, our findings demonstrate that GSAP cleavage via caspase-3 is regulated and depend upon the availability of 5LO further establishing this protein as an attractive and viable therapeutic target for Alzheimer's disease. ..
  85. Häfner A, Cernescu M, Hofmann B, Ermisch M, Hörnig M, Metzner J, et al. Dimerization of human 5-lipoxygenase. Biol Chem. 2011;392:1097-111 pubmed publisher
    ..This interface domain was confirmed by the observation that 5-LO dimer formation and inhibition of activity by diamide was largely prevented when four cysteines (C159S, C300S, C416S, C418S) in this domain were mutated to serines. ..
  86. Njoroge S, Seegmiller A, Katrangi W, Laposata M. Increased ?5- and ?6-desaturase, cyclooxygenase-2, and lipoxygenase-5 expression and activity are associated with fatty acid and eicosanoid changes in cystic fibrosis. Biochim Biophys Acta. 2011;1811:431-40 pubmed publisher
  87. Dolinska M, Piccini A, Wong W, Gelali E, Johansson A, Klang J, et al. Leukotriene signaling via ALOX5 and cysteinyl leukotriene receptor 1 is dispensable for in vitro growth of CD34+CD38- stem and progenitor cells in chronic myeloid leukemia. Biochem Biophys Res Commun. 2017;490:378-384 pubmed publisher
    ..In an experimental mouse CML model system, the leukotriene pathway, and specifically, the expression ALOX5, encoding 5-lipoxygenase (5-LO), has been reported as a critical regulator of the LSC...
  88. Balistreri C, Caruso C, Carruba G, Miceli V, Campisi I, Listi F, et al. A pilot study on prostate cancer risk and pro-inflammatory genotypes: pathophysiology and therapeutic implications. Curr Pharm Des. 2010;16:718-24 pubmed
    ..Overall, the present results suggest the likely association of these SNPs and PC risk, clearly motivating the need of larger studies to confirm the role of these genes in PC development and/or progression. ..
  89. Mandal A, Jones P, Bair A, Christmas P, Miller D, Yamin T, et al. The nuclear membrane organization of leukotriene synthesis. Proc Natl Acad Sci U S A. 2008;105:20434-9 pubmed publisher
    ..We also identify these complexes in mouse neutrophils isolated from inflamed joints. Our studies reveal the macromolecular organization of LT synthesis. ..
  90. Poole E, Bigler J, Whitton J, Sibert J, Potter J, Ulrich C. Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms and risk of colorectal polyps. Cancer Epidemiol Biomarkers Prev. 2006;15:502-8 pubmed
    Prostacyclin synthase (PGIS) and arachidonate 5-lipoxygenase (ALOX5) are enzymes relevant to prostaglandin and leukotriene synthesis, both important pathways for colon cancer risk...