Genomes and Genes
Summary: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates. These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids. The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- .
- Vacas M, Keller Sarmiento M, Etchegoyen G, Pereyra E, Gimeno M, Cardinali D. Involvement of 5-lipoxygenase pathway in norepinephrine stimulation of rat pineal melatonin synthesis. Neuroendocrinology. 1987;46:412-6 pubmed..These results suggest that the 5-lipoxygenase pathway plays a significant role in NE-stimulated melatonin production by the rat pineal gland. ..
- Varjas T, Nowrasteh G, Budán F, Horvath G, Cseh J, Gyöngyi Z, et al. The effect of fenugreek on the gene expression of arachidonic acid metabolizing enzymes. Phytother Res. 2011;25:221-7 pubmed publisher..In COX1 gene, the fenugreek diet could suppress the expression, except for spleen, independently from carcinogen exposure. Therefore by inhibiting the arachidonic acid metabolism fenugreek may prevent tumorigenesis...
- Ueda N, Hiroshima A, Natsui K, Shinjo F, Yoshimoto T, Yamamoto S, et al. Localization of arachidonate 12-lipoxygenase in parenchymal cells of porcine anterior pituitary. J Biol Chem. 1990;265:2311-6 pubmed..These biochemical and immunohistochemical results provide a good reason for considering that 12-lipoxygenase does play an important role in pituitary function. ..
- Rouzer C, Samuelsson B. Reversible, calcium-dependent membrane association of human leukocyte 5-lipoxygenase. Proc Natl Acad Sci U S A. 1987;84:7393-7 pubmed..Ca2+ also caused a destabilization of the 5-lipoxygenase. Homogenates prepared in the presence of Ca2+ contained lower total enzyme activity, and retention of activity in these samples over time was also diminished. ..
- 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. ..
- Robak J, Shridi F, Wolbiś M, Krolikowska M. Screening of the influence of flavonoids on lipoxygenase and cyclooxygenase activity, as well as on nonenzymic lipid oxidation. Pol J Pharmacol Pharm. 1988;40:451-8 pubmed..A good correlation between the chemical structure and the tested activity was observed. The most active compounds in all tests were luteolin, 6-hydroxyluteolin, nepetin, quercetagetin, patuletin and myricetin. ..
- Maruyama T, Ueda N, Yoshimoto T, Yamamoto S, Komatsu N, Watanabe K. Immunohistochemical study of arachidonate 12-lipoxygenase in porcine tissues. J Histochem Cytochem. 1989;37:1125-31 pubmed..In these organs, resident mast cells and granulocytes infiltrating the interstitial tissues were positively immunostained. The enzyme was not detected in parenchymal cells of these organs under our experimental conditions. ..
- Chang W, Nakao J, Orimo H, Murota S. Effects of reduced glutathione on the 12-lipoxygenase pathways in rat platelets. Biochem J. 1982;202:771-6 pubmed..Fractionation of cell homogenates indicates that the cytosol fraction possesses almost all the 12-lipoxygenase activity, whereas the microsomal fraction exhibits little enzyme activity. ..
- Tieman T, Steel D, Gor Y, Kehoe J, Schwartz J, Feinmark S. A pertussis toxin-sensitive 8-lipoxygenase pathway is activated by a nicotinic acetylcholine receptor in aplysia neurons. J Neurophysiol. 2001;85:2150-8 pubmed..Our results are consistent with the idea that the nicotinic ACh receptor that activates the sustained chloride conductance can, independent of the chloride ion influx, initiate lipid messenger synthesis. ..
- Prosiegel M, Neu I, Mallinger J, Wildfeuer A, Mehlber L, Vogl S, et al. Suppression of experimental autoimmune encephalomyelitis by dual cyclo-oxygenase and 5-lipoxygenase inhibition. Acta Neurol Scand. 1989;79:223-6 pubmed..Therefore, the application of leukotriene inhibitors could contribute to the future treatment of MS. ..
- Foley T. 5-HPETE is a potent inhibitor of neuronal Na+, K(+)-ATPase activity. Biochem Biophys Res Commun. 1997;235:374-6 pubmed..It is proposed that 5-HPETE production by 5-lipoxygenase and subsequent inhibition of neuronal Na+, K(+)-ATPase activity may be a mechansim for modulating synaptic transmission. ..
- Anderson K, Ondrey F, Harris J. Do lipoxygenases modulate normal or aberrant lympho-hematopoiesis?. Leuk Res. 1999;23:51-6 pubmed..Recent evidence concerning these questions is reviewed and some reasons for these difficulties are considered. ..
- Coffa G, Hill E. Discovery of an 11 (R)- and 12(S)-lipoxygenase activity in ovaries of the mussel Mytilus edulis. Lipids. 2000;35:1195-204 pubmed..This study shows that female gonads of the mussel express an 11(R)- and 12(S)-lipoxygenase activity whose expression is dependent on differentiation of the ovary. ..
- Jisaka M, Boeglin W, Kim R, Brash A. Site-directed mutagenesis studies on a putative fifth iron ligand of mouse 8S-lipoxygenase: retention of catalytic activity on mutation of serine-558 to asparagine, histidine, or alanine. Arch Biochem Biophys. 2001;386:136-42 pubmed..We conclude that mouse 8-LOX is catalytically competent with only four amino acid iron ligands, and that Ser-558 of the wild-type enzyme does not play an essential role in catalysis. ..
- Jaschonek K, Steinhilber D, Einsele H, Ehninger G, Roth H. 5-Lipoxygenase inhibition by antifungal azole derivatives: new tools for immunosuppression?. Eicosanoids. 1989;2:189-90 pubmed..In contrast, fluconazole, an antifungal agent with bistriazole structure, had no effect on the Ca2+ ionophore A 23187-induced formation of 5-lipoxygenase metabolites in PMNL. ..
- Daret D, Blin P, Larrue J. Synthesis of hydroxy fatty acids from linoleic acid by human blood platelets. Prostaglandins. 1989;38:203-14 pubmed..Since these compounds remained essentially associated with the platelets, their presence may significantly participate in the mechanisms of platelet activation. ..
- Johnson H, Stout B, Ruppel P. Inhibition of the 5-lipoxygenase pathway with piriprost (U-60,257) protects normal primates from ozone-induced methacholine hyperresponsive small airways. Prostaglandins. 1988;35:459-66 pubmed
- White D, Basbaum A, Goetzl E, Levine J. The 15-lipoxygenase product, 8R,15S-diHETE, stereospecifically sensitizes C-fiber mechanoheat nociceptors in hairy skin of rat. J Neurophysiol. 1990;63:966-70 pubmed..5. 8R,15S-diHETE also sensitized C-MHs (n = 9) to a thermal stimulus consisting of 37 degrees C for 5 min.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Mori M, Izumi T, Shimizu T. Energy-dependent export of leukotriene B4 in Xenopus oocytes. Biochim Biophys Acta. 1993;1168:23-9 pubmed..It was thus shown that the two potent lipid mediators are exported from cells in a different manner and that oocytes are a good model for analyzing export systems for bioactive mediators. ..
- Jin J, Boeglin W, Cha J, Brash A. 8R-Lipoxygenase-catalyzed synthesis of a prominent cis-epoxyalcohol from dihomo-?-linolenic acid: a distinctive transformation compared with S-lipoxygenases. J Lipid Res. 2012;53:292-9 pubmed publisher..This characteristic and the synthesis of cis-epoxy epoxyalcohol may be a feature of R-specific lipoxygenases. ..
- Peters Golden M, Shelly C. Inhibition of alveolar macrophage 5-lipoxygenase metabolism by auranofin. Biochem Pharmacol. 1989;38:1589-95 pubmed..These data indicate that, at therapeutic concentrations, AF acts in vitro as a selective inhibitor of macrophage 5-lipoxygenase metabolism. This likely represents an important mechanism of action of AF in chronic inflammatory disorders. ..
- Moroney M, Alcaraz M, Forder R, Carey F, Hoult J. Selectivity of neutrophil 5-lipoxygenase and cyclo-oxygenase inhibition by an anti-inflammatory flavonoid glycoside and related aglycone flavonoids. J Pharm Pharmacol. 1988;40:787-92 pubmed..These results are discussed in relation to possible mechanisms of hypolaetin-8-glucoside's protective actions and the concept that these inhibitory effects of flavonoids cannot be ascribed to a unitary free radical scavenging action. ..
- Ohuchi K, Takahashi C, Hirasawa N, Watanabe M, Fujiki H, Tsurufuji S. Stimulation of histamine release and arachidonic acid metabolism in rat peritoneal mast cells by thapsigargin, a non-TPA-type tumor promoter. Biochim Biophys Acta. 1989;1003:9-14 pubmed..Time-course experiments of histamine release and the release of radioactivity from [3H]arachidonic acid-labeled mast cells also provide evidence for a difference in mechanism. ..
- Riendeau D, Denis D, Choo L, Nathaniel D. Stimulation of 5-lipoxygenase activity under conditions which promote lipid peroxidation. Biochem J. 1989;263:565-72 pubmed..They also indicate that stimulation of 5-lipoxygenase activity can contribute to increase lipid peroxidation in iron and nucleotide-promoted reactions. ..
- De Vries G, Amdahl L, Mobasser A, Wenzel M, Wheeler L. Preferential inhibition of 5-lipoxygenase activity by manoalide. Biochem Pharmacol. 1988;37:2899-905 pubmed..These data indicate that manoalide is a selective 5-LO inhibitor and suggest the possibility that its anti-inflammatory actions may be due, at least in part, to inhibition of leukotriene synthesis. ..
- Fruteau de Laclos B, Borgeat P. Conditions for the formation of the oxo derivatives of arachidonic acid from platelet 12-lipoxygenase and soybean 15-lipoxygenase. Biochim Biophys Acta. 1988;958:424-33 pubmed..5: 1.5 from 12-HPETE incubated with hematin (150 nM), 15-ketoeicosatetraenoic acid was the only carbonyl compound generated from 15-HPETE in the same conditions, emphasizing the unique reactivity of the 12-HPETE. ..
- Shimizu T, Watanabe T, Asano T, Seyama Y, Takakura K. Activation of the arachidonate 5-lipoxygenase pathway in the canine basilar artery after experimental subarachnoidal hemorrhage. J Neurochem. 1988;51:1126-31 pubmed..1 nmol 5-HETE/5 min/mg of protein) after subarachnoidal hemorrhage. The observation that fatty acid hydroperoxides stimulated the 5-lipoxygenase activity indicates a possible role of lipid peroxides in the development of vasospasm. ..
- Walstra P, Verhagen J, Vermeer M, Veldink G, Vliegenthart J. Demonstration of a 12-lipoxygenase activity in bovine polymorphonuclear leukocytes. Biochim Biophys Acta. 1987;921:312-9 pubmed
- McColl S, Krump E, Naccache P, Caon A, Borgeat P. Activation of the human neutrophil 5-lipoxygenase by exogenous arachidonic acid: involvement of pertussis toxin-sensitive guanine nucleotide-binding proteins. Br J Pharmacol. 1989;97:1265-73 pubmed..6. These results imply that exogenous arachidonic acid is not only used as a substrate, but also activates the 5-lipoxygenase. Possible mechanisms of action are discussed. ..
- Blackham A, Griffiths R, Hallam C, Mann J, Mitchell P, Norris A, et al. FPL 62064, a topically active 5-lipoxygenase/cyclooxygenase inhibitor. Agents Actions. 1990;30:432-42 pubmed..Co-injected with arachidonic acid in rabbit skin, FPL 62064 inhibited oedema and eicosanoid formation. ..
- Flament J, Schandene L, Boeynaems J. Effect of the 5-lipoxygenase inhibitor piriprost on superoxide production by human neutrophils. Prostaglandins Leukot Essent Fatty Acids. 1988;34:175-80 pubmed
- Hecker M, Ullrich V. 12(S)-Hydroxy-5,8,10 (Z,E,E)-heptadecatrienoic acid (HHT) is preferentially metabolized to its 12-keto derivative by human erythrocytes in vitro. Eicosanoids. 1988;1:19-25 pubmed..The potential use of KHT for monitoring thromboxane synthase activity in vivo is discussed. ..
- Furstenberger G, Hagedorn H, Jacobi T, Besemfelder E, Stephan M, Lehmann W, et al. Characterization of an 8-lipoxygenase activity induced by the phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate in mouse skin in vivo. J Biol Chem. 1991;266:15738-45 pubmed..5-8.0. 8-HPETE/8-HETE levels in mouse epidermis in vivo were determined by gas chromatography-mass spectrometry and found to be strongly increased after phorbol ester treatment, in agreement with the induction of 8-lipoxygenase observed. ..
- Vanderhoek J. Role of the 15-lipoxygenase in the immune system. Ann N Y Acad Sci. 1988;524:240-51 pubmed..Several stimuli, including HETEs, can convert the inactive 15-LO to an active species that can metabolize AA to a variety of products. Many of these metabolites have been reported to modulate various components of the immune response. ..
- Warner J, Lichtenstein L, MacGlashan D. Effects of a specific inhibitor of the 5-lipoxygenase pathway on mediator release from human basophils and mast cells. J Pharmacol Exp Ther. 1988;247:218-22 pubmed..The specificity of the drug for the 5-lipoxygenase pathway was confirmed in three experiments with human lung mast cells.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- 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. ..
- Minich W, Evdokimova V, Oleinikov A, Hohne M, Thiele B, Rapoport S. Evidence for the appearance of a reticulocyte population low in lipoxygenase mRNA during the recovery from a phenylhydrazine-induced anemia in rabbits. FEBS Lett. 1989;245:127-30 pubmed..A cell-free system prepared from the recovery-reticulocytes exhibits low endogenous synthesis of non-globin polypeptides, even without nuclease treatment, but retains full capacity to be stimulated by exogenous mRNA. ..
- Green F. Generation and metabolism of lipoxygenase products in normal and membrane-damaged cultured human keratinocytes. J Invest Dermatol. 1989;93:486-91 pubmed
- Mylari B, Carty T, Moore P, Zembrowski W. 1,2-Dihydro-1-oxopyrrolo[3,2,1-kl]phenothiazine-2-carboxamides and congeners, dual cyclooxygenase/5-lipoxygenase inhibitors with antiinflammatory activity. J Med Chem. 1990;33:2019-24 pubmed..4 microM, respectively. It was active in the rat foot edema test for antiinflammatory effect (48% inhibition at 33 mg/kg po) and in the mouse phenylbenzoquinone induced writhing test for analgesic effect (93% inhibition at 32 mg/kg po). ..
- Duell E, Ellis C, Voorhees J. Determination of 5,12, and 15-lipoxygenase products in keratomed biopsies of normal and psoriatic skin. J Invest Dermatol. 1988;91:446-50 pubmed..From a single keratome biopsy, multiple eicosanoids can be separated and quantitated; in addition, levels before, during, and after therapy for psoriasis may be compared. ..
- Jones T, Charette L, Denis D. Leukotriene and anti-IgE induced contractions of human isolated trachea: studies with leukotriene receptor antagonists and a novel 5-lipoxygenase inhibitor. Can J Physiol Pharmacol. 1988;66:762-8 pubmed..LTD4 antagonists, such as L-648,051, may be useful in assessing the role of leukotrienes in respiratory disease. ..
- Edwin S, Mitchell M. Arachidonate lipoxygenase metabolite formation in gestational tissues. J Lipid Mediat Cell Signal. 1994;9:291-300 pubmed..We postulate that activation of protein kinase C can result in enhanced production of arachidonate lipoxygenase metabolites that may have actions on the parturient process. ..
- Flavin D. A lipoxygenase inhibitor in breast cancer brain metastases. J Neurooncol. 2007;82:91-3 pubmed..The results suggest a potential new area of therapy for breast cancer patients with brain metastases that may be useful as an adjuvant to our standard therapy. ..
- Kargman S, Rouzer C. Studies on the regulation, biosynthesis, and activation of 5-lipoxygenase in differentiated HL60 cells. J Biol Chem. 1989;264:13313-20 pubmed..Finally, additional 5-lipoxygenase was able to translocate to the membrane in response to subsequent ionophore challenges. ..
- Buckle D, Bumstead J, Clarke G, Foster K, Parr H, Taylor J, et al. Inhibition of mammalian 5-lipoxygenase by 2-benzylaminophenols. Prostaglandins Leukot Essent Fatty Acids. 1988;33:29-33 pubmed..Two compounds evaluated for their effects on anaphylactic contractions in isolated human lung were shown to attenuate the leukotriene-induced component of the response. ..
- Sperling R, Austen K. Regulation of the 5-lipoxygenase pathway in human leucocytes. Br J Rheumatol. 1988;27:469-76 pubmed..A more comprehensive understanding of the regulation and modulation of the 5-lipoxygenase pathway may result in more effective management of inflammatory and immune disorders. ..
- Romero R, Quintero R, Emamian M, Wan M, Grzyboski C, Hobbins J, et al. Arachidonate lipoxygenase metabolites in amniotic fluid of women with intra-amniotic infection and preterm labor. Am J Obstet Gynecol. 1987;157:1454-60 pubmed..These results suggest that the amniotic fluid concentrations of arachidonate lipoxygenase metabolites are affected differently by the presence of infection and labor in women with premature rupture of membranes. ..
- Medina J, Odlander B, Funk C, Fu J, Claesson H, Radmark O. B-lymphocytic cell line Raji expresses the leukotriene A4 hydrolase gene but not the 5-lipoxygenase gene. Biochem Biophys Res Commun. 1989;161:740-5 pubmed..Thus, the genes coding for the two enzymes required for biosynthesis of leukotriene B4 from arachidonic acid, 5-lipoxygenase and LTA4 hydrolase, were differentially expressed in the Raji cells. ..
- Turk J, Wolf B, Easom R, Hughes J, McDaniel M. Arachidonic acid metabolism in isolated pancreatic islets. V. The enantiomeric composition of 12-hydroxy-5,8,10,14-eicosatetraenoic acid indicates synthesis by a 12-lipoxygenase rather than a monooxygenase. Biochim Biophys Acta. 1989;1001:16-24 pubmed..These findings suggest that islet 12-HETE is a product of a 12-lipoxygenase rather than of a cytochrome P-450 monooxygenase and further implicate 12-lipoxygenase products in stimulus-secretion coupling. ..
- Kudryavtsev I, Gudkova M, Pavlova O, Oreshkin A, Myasishcheva N. Lipoxygenase pathway of arachidonic acid metabolism in growth control of tumor cells of different type. Biochemistry (Mosc). 2005;70:1396-403 pubmed..Treatment of these cultures with 12-HETE virtually restored the growth potential of the tumor cells. The findings suggest that the lipoxygenase metabolite of AA, 12-HETE, is a growth-limiting factor for tumor cells of definite type. ..
- Yu Z, Schneider C, Boeglin W, Brash A. Epidermal lipoxygenase products of the hepoxilin pathway selectively activate the nuclear receptor PPARalpha. Lipids. 2007;42:491-7 pubmed..Formation of a ligand for the nuclear receptor PPARalpha may be one possibility by which 12R-LOX and eLOX3 contribute to epidermal differentiation. ..
- Nagase T, Fukuchi Y, Jo C, Teramoto S, Uejima Y, Ishida K, et al. Endothelin-1 stimulates arachidonate 15-lipoxygenase activity and oxygen radical formation in the rat distal lung. Biochem Biophys Res Commun. 1990;168:485-9 pubmed..Thus, endothelin-1 may contribute to the inflammatory and hyperreactive process of lungs, by enhancing the release of 15-hydroxyeicosatetraenoic acid and oxygen radicals in the distal lung unit. ..
- Green F. In vivo generation of 5-lipoxygenase products in frogs and toads. Biochem Biophys Res Commun. 1987;148:1533-9 pubmed..These observations of in vivo eicosanoid production confirm the participation of 5-lipoxygenase activity in the inflammatory response to infection. ..