Genomes and Genes
Gene Symbol: 5 lipoxygenase
Description: arachidonate 5-lipoxygenase
Alias: LOX5A, arachidonate 5-lipoxygenase, 5 - Lipoxygenase, 5-LO, 5-lipoxygenase
Products: 5 lipoxygenase
- Escoubet Lozach L, M Rini C, Rey A, Beraud M, Lepert J, Courtade M, et al. Increased expression of cytosolic phospholipase A2, 5-lipoxygenase and 5-lipoxygenase-activating protein in rat peritoneal macrophages during ovalbumin-induced sensitization. Clin Exp Allergy. 2001;31:1094-104 pubmed..Our results also suggest that IL-4 is not the major element originating the enzymatic modification induced by sensitization in peritoneal macrophages. ..
- Ram A, Singh S, Singh V, Kumar S, Ghosh B. Inhaled carbenoxolone prevents allergic airway inflammation and airway hyperreactivity in a mouse model of asthma. Int Arch Allergy Immunol. 2009;149:38-46 pubmed publisher..00061) in sera. 5-LO expression was also markedly reduced. However, corticosterone levels were not affected. Inhaled CBX alleviates the asthmatic features in mice and could be a potent nebulized therapy in clinical asthma. ..
- Herb F, Thye T, Niemann S, Browne E, Chinbuah M, Gyapong J, et al. ALOX5 variants associated with susceptibility to human pulmonary tuberculosis. Hum Mol Genet. 2008;17:1052-60 pubmed publisher..003, OR 1.50). Our observation of an association of ALOX5 variants with susceptibility to TB contributes evidence of the importance of 5-LO products to the regulation of immune responses to M. tuberculosis. ..
- Henderson W, Lewis D, Albert R, Zhang Y, Lamm W, Chiang G, et al. The importance of leukotrienes in airway inflammation in a mouse model of asthma. J Exp Med. 1996;184:1483-94 pubmed..The role of leukotrienes or eosinophils in mediating airway hyperresponsiveness to aeroallergen could not be established, however, in this murine model. ..
- Caironi P, Ichinose F, Liu R, Jones R, Bloch K, Zapol W. 5-Lipoxygenase deficiency prevents respiratory failure during ventilator-induced lung injury. Am J Respir Crit Care Med. 2005;172:334-43 pubmed..These results indicate that LTs play a central role in the lung injury and impaired oxygenation induced by HVT ventilation. ..
- Failla M, Genovese T, Mazzon E, Gili E, Muià C, Sortino M, et al. Pharmacological inhibition of leukotrienes in an animal model of bleomycin-induced acute lung injury. Respir Res. 2006;7:137 pubmed..Given our results as well as those coming from genetic studies, it might be considered meaningful to trial this drug class in the treatment of pulmonary fibrosis, a disease that still represents a major challenge to medical treatment. ..
- Polito F, Bitto A, Irrera N, Squadrito F, Fazzari C, Minutoli L, et al. Flavocoxid, a dual inhibitor of cyclooxygenase-2 and 5-lipoxygenase, reduces pancreatic damage in an experimental model of acute pancreatitis. Br J Pharmacol. 2010;161:1002-11 pubmed publisher..Flavocoxid may provide a potential therapeutic approach to the treatment of patients at high risk of developing this life-threatening condition. ..
- Yuan H, Reddy M, Deshpande S, Jia Y, Park J, Lanting L, et al. Epigenetic Histone Modifications Involved in Profibrotic Gene Regulation by 12/15-Lipoxygenase and Its Oxidized Lipid Products in Diabetic Nephropathy. Antioxid Redox Signal. 2016;24:361-75 pubmed publisher..Targeting 12/15-LO might be a useful strategy to inhibit key epigenetic mechanisms involved in DN. ..
- Gross N, Holloway N, Narine K. Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis. Radiat Res. 1991;127:317-24 pubmed
- Coffey M, Phare S, Peters Golden M. Induction of inducible nitric oxide synthase by lipopolysaccharide/interferon gamma and sepsis down-regulates 5-lipoxygenase metabolism in murine alveolar macrophages. Exp Lung Res. 2004;30:615-33 pubmed..iNOS knock-out mice were protected from the decrease in alveolar macrophage 5-lipoxygenase metabolism. iNOS regulates alveolar macrophage 5-lipoxygenase metabolism following endotoxin exposure. ..
- 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. ..
- Chen C, Voelkel N, Chang S. Platelet-activating factor potentiates protamine-induced lung edema. Role of eicosanoids. Am J Respir Crit Care Med. 1994;149:34-40 pubmed..We conclude that both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism are involved in PAF-induced potentiation of protamine lung edema. ..
- Stringham J, Moore E, Gamboni F, Harr J, Fragoso M, Chin T, et al. Mesenteric lymph diversion abrogates 5-lipoxygenase activation in the kidney following trauma and hemorrhagic shock. J Trauma Acute Care Surg. 2014;76:1214-21 pubmed publisher..These data suggest that gut-derived leukotriene substrate predisposes the kidney and the lung to subsequent injury. ..
- Strid T, Svartz J, Franck N, Hallin E, Ingelsson B, Soderstrom M, et al. Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein. Biochem Biophys Res Commun. 2009;381:518-22 pubmed publisher..Direct interaction of 5-LO and LTC(4)S in ionophore-stimulated (but not un-stimulated) cells was demonstrated by BRET using GFP-5-LO and Rluc-LTC(4)S. ..
- Raychaudhuri A, Chertock H, Chovan J, Jones L, Kimble E, Kowalski T, et al. Inhibition of LTB4 biosynthesis in situ by CGS 23885, a potent 5-lipoxygenase inhibitor, correlates with its pleural fluid concentrations in an experimentally induced rat pleurisy model. Naunyn Schmiedebergs Arch Pharmacol. 1997;355:470-4 pubmed..The results confirm that CGS 23885 is a specific, orally active 5-LO inhibitor which can achieve concentrations in the pleural cavity sufficient to inhibit production of LTB4 and LTC4/D4/E4 in an ongoing inflammatory response. ..
- Minor W, Steczko J, Bolin J, Otwinowski Z, Axelrod B. Crystallographic determination of the active site iron and its ligands in soybean lipoxygenase L-1. Biochemistry. 1993;32:6320-3 pubmed..A sixth protein ligand is not present, and the sixth coordination site opens into a wide cleft. The structure of the soybean lipoxygenase was solved by multiple anomalous isomorphous replacements. ..
- Luo M, Pang C, Gerken A, Brock T. Multiple nuclear localization sequences allow modulation of 5-lipoxygenase nuclear import. Traffic. 2004;5:847-54 pubmed..Multiple NLSs on other proteins may likewise allow fine control of protein action through modulation of the level of import. ..
- Coreno A, Skowronski M, Kotaru C, McFadden E. Comparative effects of long-acting beta2-agonists, leukotriene receptor antagonists, and a 5-lipoxygenase inhibitor on exercise-induced asthma. J Allergy Clin Immunol. 2000;106:500-6 pubmed..The synthesis inhibitor zileuton affords a comparable magnitude of prophylaxis but has a considerably shorter duration of action. ..
- Hennig R, Grippo P, Ding X, Rao S, Buchler M, Friess H, et al. 5-Lipoxygenase, a marker for early pancreatic intraepithelial neoplastic lesions. Cancer Res. 2005;65:6011-6 pubmed..These findings provide evidence that 5-LOX plays a key role in the development of pancreatic cancer. Furthermore, the lipoxygenase pathway may be a target for the prevention of this devastating disease. ..
- Kalayci O, Birben E, Sackesen C, Keskin O, Tahan F, Wechsler M, et al. ALOX5 promoter genotype, asthma severity and LTC production by eosinophils. Allergy. 2006;61:97-103 pubmed..05 for both). Our results suggest that children who express the asthma phenotype despite having a genetic variant that impairs their ability to express ALOX5 have more severe disease and thus are more likely to have asthma symptoms. ..
- Möbius C, Aust G, Wiedmann M, Wittekind C, Mossner J, Hauss J, et al. Prognostic value of eicosanoid pathways in extrahepatic cholangiocarcinoma. Anticancer Res. 2008;28:873-8 pubmed
- Balcarek J, Theisen T, Cook M, Varrichio A, Hwang S, Strohsacker M, et al. Isolation and characterization of a cDNA clone encoding rat 5-lipoxygenase. J Biol Chem. 1988;263:13937-41 pubmed..The cDNA recognizes a 2.6-kb mRNA species which is detected in all tissues but is particularly abundant in RNA from lung. ..
- Graupera M, Garcia Pagan J, Titos E, Claria J, Massaguer A, Bosch J, et al. 5-lipoxygenase inhibition reduces intrahepatic vascular resistance of cirrhotic rat livers: a possible role of cysteinyl-leukotrienes. Gastroenterology. 2002;122:387-93 pubmed..Our results suggest that 5-lipoxygenase-derived eicosanoids may contribute to the increased intrahepatic vascular resistance of cirrhotic rat livers and therefore the pathogenesis of portal hypertension. ..
- Bai C, Matsui E, Ohnishi H, Kimata K, Kasahara K, Kaneko H, et al. A novel polymorphism, E254K, in the 5-lipoxygenase gene associated with bronchial asthma. Int J Mol Med. 2008;21:139-44 pubmed..Thus, our results suggest that E254K in the 5-LO might be associated with BA. ..
- Jones S, Luo M, Healy A, Peters Golden M, Brock T. Structural and functional criteria reveal a new nuclear import sequence on the 5-lipoxygenase protein. J Biol Chem. 2002;277:38550-6 pubmed..Moreover, we suggest that another sequence that can mediate nuclear import of 5-lipoxygenase remains to be identified. ..
- Tu X, Yang W, Wang C, Shi S, Zhang Y, Chen C, et al. Zileuton reduces inflammatory reaction and brain damage following permanent cerebral ischemia in rats. Inflammation. 2010;33:344-52 pubmed publisher..The neuroprotective effect of zileuton in cerebral ischemia might be associated with the inhibition of inflammatory reaction. ..
- Zhang X, Zhang L, Li C, Chen W, Zhao J, Wei E. [5-lipoxygenase is involved in rotenone-induced injury in PC12 cells]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2011;40:150-5 pubmed..5-LOX is involved in rotenone-induced injury in PC12 cells, and 5-LOX inhibitor zileuton can reduce rotenone-induced 5-LOX activation and cell injury. ..
- 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. ..
- Brock T. Down-regulation of 5-lipoxygenase activity and leukotriene production by prolonged exposure to lipopolysaccharide. Adv Exp Med Biol. 2002;507:101-5 pubmed
- Kang J, Kim N, Kim B, Kim J, Lee B, Park J, et al. Gastroprotective action of Cochinchina momordica seed extract is mediated by activation of CGRP and inhibition of cPLA(2)/5-LOX pathway. Dig Dis Sci. 2009;54:2549-60 pubmed publisher..Furthermore, CGRP-NO pathway was found to play an important role in these gastroprotective effects of SK-MS10...
- 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. ..
- Hosford G, Koyanagi K, Leung W, Olson D. Hyperoxia increases protein mass of 5-lipoxygenase and its activating protein, flap, and leukotriene B(4) output in newborn rat lungs. Exp Lung Res. 2002;28:671-84 pubmed..These data show that hyperoxia increases LTB(4) output, as well as protein levels of 5-LO and FLAP, in newborn rat lungs during early postnatal life. Elevated LTB(4) may contribute to the etiology of newborn lung disease. ..
- Jones J, Walker J, Song Y, Weiss N, Cardoso W, Tuder R, et al. Effect of 5-lipoxygenase on the development of pulmonary hypertension in rats. Am J Physiol Heart Circ Physiol. 2004;286:H1775-84 pubmed..These data suggest that 5-LO plays a critical role in the progression of pulmonary hypertension in rats and that the detrimental effect of 5-LO is manifest only in the setting of pulmonary vascular endothelial cell dysfunction. ..
- Cortes Burgos L, Zweifel B, Settle S, Pufahl R, Anderson G, Hardy M, et al. CJ-13610, an orally active inhibitor of 5-lipoxygenase is efficacious in preclinical models of pain. Eur J Pharmacol. 2009;617:59-67 pubmed publisher..6, 2 and 6 mg/kg/day reversed two modalities of pain in this model; tactile allodynia and weight bearing differential. Taken together, these data suggest that 5-LOX pathway and the leukotriene products are important mediators of pain. ..
- Tong W, Ding X, Witt R, Adrian T. Lipoxygenase inhibitors attenuate growth of human pancreatic cancer xenografts and induce apoptosis through the mitochondrial pathway. Mol Cancer Ther. 2002;1:929-35 pubmed..LOX inhibitors are likely to be valuable for the treatment of human pancreatic cancer. ..
- Edmiston J, Lebman D. A transforming growth factor-beta regulable RNA-binding protein interacts specifically with germline Ig alpha transcripts. Int Immunol. 1997;9:427-33 pubmed
- Ge Q, Wei E, Zhang W, Hu X, Huang X, Zhang L, et al. Activation of 5-lipoxygenase after oxygen-glucose deprivation is partly mediated via NMDA receptor in rat cortical neurons. J Neurochem. 2006;97:992-1004 pubmed..From these results, we conclude that OGD can activate 5-LOX in primary rat cortical neurons, and that this activation may be partly mediated via activating NMDA receptor. ..
- 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
- Lisovyy O, Dosenko V, Nagibin V, Tumanovska L, Korol M, Surova O, et al. Cardioprotective effect of 5-lipoxygenase gene (ALOX5) silencing in ischemia-reperfusion. Acta Biochim Pol. 2009;56:687-94 pubmed..05) resulted in a 3.8-fold reduction of infarct size in an open chest rat model of heart IR (P < 0.05). Thus, RNAi targeting of ALOX5 protects heart cells against IR injury both in culture and in vivo. ..
- Choi K, Kim E, Hong H, Ock C, Lee J, Kim J, et al. Attenuation of cysteamine-induced duodenal ulcer with Cochinchina momordica seed extract through inhibiting cytoplasmic phospholipase A2/5-lipoxygenase and activating ?-glutamylcysteine synthetase. J Gastroenterol Hepatol. 2012;27 Suppl 3:13-22 pubmed publisher..This study was aimed to document the preventive effects of Cochinchina momordica seed extract against cysteamine-induced duodenal ulcer as well as the elucidation of its pharmacological mechanisms...
- Lee D, Kwak I, Lee S, Song S, Seong E, Yang B, et al. Post-treatment effects of erythropoietin and nordihydroguaiaretic acid on recovery from cisplatin-induced acute renal failure in the rat. J Korean Med Sci. 2009;24 Suppl:S170-5 pubmed publisher..Those PCNA(+) cells were significantly increased in Cisplatin+NDGA group. These results suggest that EPO and also NDGA accelerate renal function recovery by stimulating tubular epithelial cell regeneration. ..
- Koshino T, Takano S, Houjo T, Sano Y, Kudo K, Kihara H, et al. Expression of 5-lipoxygenase and 5-lipoxygenase-activating protein mRNAs in the peripheral blood leukocytes of asthmatics. Biochem Biophys Res Commun. 1998;247:510-3 pubmed..These data suggest that up-regulation of 5-LO and FLAP mRNAs might be involved in the increased leukotriene synthesis and play an important role in the pathogenesis of asthma. ..
- Plewako H, Holmberg K, Oancea I, Rak S. Increased expression of lipoxygenase enzymes during pollen season in nasal biopsies of pollen-allergic patients. Allergy. 2006;61:725-30 pubmed..02; P=0.01; P=0.03 respectively). In sensitized patients exposure to pollen allergen results in increased expression of enzymes of the eicosanoid pathway. ..
- Coffey M, Phare S, Peters Golden M. Interaction between nitric oxide, reactive oxygen intermediates, and peroxynitrite in the regulation of 5-lipoxygenase metabolism. Biochim Biophys Acta. 2002;1584:81-90 pubmed..Zileuton reduced ROI generation in LPS-treated cells. These studies identify an important role for ROI and ONOO(-) in the suppression of 5-LO metabolism by LPS. ..
- Ye Y, Lin Y, Perez Polo J, Uretsky B, Ye Z, Tieu B, et al. Phosphorylation of 5-lipoxygenase at ser523 by protein kinase A determines whether pioglitazone and atorvastatin induce proinflammatory leukotriene B4 or anti-inflammatory 15-epi-lipoxin a4 production. J Immunol. 2008;181:3515-23 pubmed..The 5LO phosphorylation determines whether 15-epi-LXA(4) (anti-inflammatory) or leukotriene B(4) (inflammatory mediator) is produced. ..
- Cottrell J, O Connor J. Pharmacological inhibition of 5-lipoxygenase accelerates and enhances fracture-healing. J Bone Joint Surg Am. 2009;91:2653-65 pubmed publisher..The goal of this study was to determine if systemic inhibition of 5-lipoxygenase with an orally delivered drug could accelerate fracture-healing...
- Chen J, Bian X, Yao X, Gong W, Hu J, Chen K, et al. Nordy, a synthetic lipoxygenase inhibitor, inhibits the expression of formylpeptide receptor and induces differentiation of malignant glioma cells. Biochem Biophys Res Commun. 2006;342:1368-74 pubmed..Our results suggest that Nordy was capable of reducing the level of malignancy of glioma cells. ..
- Luchtefeld M, Drexler H, Schieffer B. 5-Lipoxygenase is involved in the angiotensin II-induced NAD(P)H-oxidase activation. Biochem Biophys Res Commun. 2003;308:668-72 pubmed..In conclusion, the present study demonstrates that ANG II enhances LTB(4)-formation in an 5-LOX dependent manner. LTB(4) activates the vascular type NAD(P)H-oxidase, leading to an increase in IL-6 transcripts. ..
- Funk C, Cao R, Zhao L, Habenicht A. Is there a role for the macrophage 5-lipoxygenase pathway in aortic aneurysm development in apolipoprotein E-deficient mice?. Ann N Y Acad Sci. 2006;1085:151-60 pubmed..We are currently exploring the potential mechanisms for 5-LO/LT involvement in aneurysm pathogenesis and if this pathway might come into play in other models such as induction by angiotensin II. ..
- Lee D, Kwak I, Lee S, Song S, Seong E, Chung H, et al. Effects of celecoxib and nordihydroguaiaretic acid on puromycin aminonucleoside-induced nephrosis in the rat. J Korean Med Sci. 2009;24 Suppl:S183-8 pubmed publisher..The present study suggested that celecoxib and NDGA might effectively reduce proteinuria in nephrotic syndrome without impairing renal function. ..
- Lefebvre B, Caron F, Bessard G, Stanke Labesque F. Effect of 5-lipoxygenase blockade on blood pressure and acetylcholine-evoked endothelium-dependent contraction in aorta from spontaneously hypertensive rats. J Hypertens. 2006;24:85-93 pubmed..These data suggested that 5-LO-derived products, through the activation of cysLT1 receptors, could be involved in the endothelium-dependent contraction to acetylcholine in aorta from SHR but not in the regulation of MABP in SHR. ..
- Segal B, Kuhns D, Ding L, Gallin J, Holland S. Thioglycollate peritonitis in mice lacking C5, 5-lipoxygenase, or p47(phox): complement, leukotrienes, and reactive oxidants in acute inflammation. J Leukoc Biol. 2002;71:410-6 pubmed..These data suggest that LTB(4) and C5a have separate but overlapping roles in thioglycollate-elicited peritonitis, and at least the leukotriene component is, in turn, regulated by reactive oxidants...
- 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. ..