Biopolym. Cell. 2015; 31(3):161-173.
http://dx.doi.org/10.7124/bc.0008DC
Огляди
Регуляція ліпоксигеназ in vivo та in vitro сполуками ліпідної природи
1Скатерна Т. Д., 1Копіч В. М., 1Харитоненко Г. І., 1Харченко О. В.
  1. Інститут біоорганічної хімії та нафтохімії НАН України
    вул. Мурманська, 1, Київ, Україна, 02660

Abstract

Ліпоксигенази (ЛО) відомі як одні з ферментів перекисного окислення ліпідів. Більшість ЛО є розчинними ферментами та характеризуються аффіністю до мембран. Транслокація ферменту з цитозолю на мембранну поверхню одна з стадій регуляції рівня продуктів ліпоксигеназного каталізу у клітині. Сорбція на мембранну поверхню описана для більшості ЛОз з рослинних та тваринних джерел. Даний огляд представляє дані по регуляції ЛОз активності природніми та хімічно модифікованими речовинами ліпідної природи. Здат­ність ліпідів регулювати ЛО активність може здійснюватись через: білок-ліпідні взаємодії C2 домену з мембраною, зміну аффінності ферменту, транслокацію ЛОз, алостеричну регуляцію, збільшення селективності до субстрату. Регуляторний вплив активної сполуки на ферментативну активність залежить від рівня ліпофільності ефекторів. При поясненні ліпоксигеназного каталізу необхідно враховувати вплив мікрооточення ферменту на рівень ЛО.
Keywords: ліпоксигеназа, алостерична регуляція, фосфоліпіди, інгібування, активація
Повний текст: (PDF, англійською)

References

[1] Rakonjac M, Fischer L, Provost P, Werz O, Steinhilber D, Samuelsson B, R?dmark O. Coactosin-like protein supports 5-lipoxygenase enzyme activity and up-regulates leukotriene A4 production. Proc Natl Acad Sci U S A. 2006;103(35):13150-5.
[2] Miller DK, Gillard JW, Vickers PJ, Sadowski S, L?veill? C, Mancini JA, Charleson P, Dixon RA, Ford-Hutchinson AW, Fortin R, et al. Identification and isolation of a membrane protein necessary for leukotriene production. Nature. 1990;343(6255):278-81.
[3] Kuhn H, Banthiya S, van Leyen K. Mammalian lipoxygenases and their biological relevance. Biochim Biophys Acta. 2015;1851(4):308-330.
[4] R?dmark O, Werz O, Steinhilber D, Samuelsson B. 5-Lipoxygenase, a key enzyme for leukotriene biosynthesis in health and disease. Biochim Biophys Acta. 2015;1851(4):331-339.
[5] Grechkin AN, Tarchevsky IA. The lipoxygenase signaling sys­tem. Russian Journal of Plant Physiology 1999; 46(1):114–23.
[6] Feussner I, Wasternack C. The lipoxygenase pathway. Annu Rev Plant Biol. 2002;53:275-97.
[7] Droillard MJ, Rouet-Mayer MA, Bureau JM, Lauriere C. Membrane-Associated and Soluble Lipoxygenase Isoforms in Tomato Pericarp (Characterization and Involvement in Membrane Alterations). Plant Physiol. 1993;103(4):1211-1219.
[8] Braidot E, Petrussa E, Micolini S, Tubaro F, Vianello A, Macr? F. Biochemical and immunochemical evidences for the presence of lipoxygenase in plant mitochondria. J Exp Bot. 2004;55(403):1655-62.
[9] Boyd RS, Jukes-Jones R, Walewska R, Brown D, Dyer MJ, Cain K. Protein profiling of plasma membranes defines aberrant signaling pathways in mantle cell lymphoma. Mol Cell Proteomics. 2009;8(7):1501-15.
[10] Peters-Golden M, Brock TG. 5-lipoxygenase and FLAP. Prostaglandins Leukot Essent Fatty Acids. 2003;69(2-3):99-109.
[11] Soberman RJ, Christmas P. The organization and consequences of eicosanoid signaling. J Clin Invest. 2003;111(8):1107-13.
[12] Dixon RA, Diehl RE, Opas E, Rands E, Vickers PJ, Evans JF, Gillard JW, Miller DK. Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis. Nature. 1990;343(6255):282-4.
[13] Jakobsson PJ, Morgenstern R, Mancini J, Ford-Hutchinson A, Persson B. Membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG). A widespread protein superfamily. Am J Respir Crit Care Med. 2000;161(2 Pt 2):S20-4.
[14] Esser J, Gehrmann U, D'Alexandri FL, Hidalgo-Est?vez AM, Wheelock CE, Scheynius A, Gabrielsson S, R?dmark O. Exosomes from human macrophages and dendritic cells contain enzymes for leukotriene biosynthesis and promote granulocyte migration. J Allergy Clin Immunol. 2010;126(5):1032-40, 1040.e1-4.
[15] Battu S, Moalic S, Rigaud M, Beneytout JL. Linoleic acid peroxidation by Solanum tuberosum lipoxygenase was activated in the presence of human 5-lipoxygenase-activating protein. Biochim Biophys Acta. 1998;1392(2-3):340-50.
[16] Noguchi M, Miyano M, Kuhara S, Matsumoto T, Noma M. Interfacial kinetic reaction of human 5-lipoxygenase. Eur J Biochem. 1994;222(2):285-92.
[17] Medkova M, Cho W. Interplay of C1 and C2 domains of protein kinase C-alpha in its membrane binding and activation. J Biol Chem. 1999;274(28):19852-61.
[18] Pande AH, Moe D, Nemec KN, Qin S, Tan S, Tatulian SA. Modulation of human 5-lipoxygenase activity by membrane lipids. Biochemistry. 2004;43(46):14653-66.
[19] Stahelin RV, Rafter JD, Das S, Cho W. The molecular basis of differential subcellular localization of C2 domains of protein kinase C-alpha and group IVa cytosolic phospholipase A2. J Biol Chem. 2003;278(14):12452-60.
[20] Jose Lopez-Andreo M, Gomez-Fernandez JC, Corbalan-Garcia S. The simultaneous production of phosphatidic acid and diacylglycerol is essential for the translocation of protein kinase Cepsilon to the plasma membrane in RBL-2H3 cells. Mol Biol Cell. 2003;14(12):4885-95.
[21] Schr?der M, H?fner AK, Hofmann B, R?dmark O, Tumulka F, Abele R, D?tsch V, Steinhilber D. Stabilisation and characterisation of the isolated regulatory domain of human 5-lipoxygenase. Biochim Biophys Acta. 2014;1842(10):1538-47.
[22] R?dmark O, Werz O, Steinhilber D, Samuelsson B. 5-Lipoxygenase, a key enzyme for leukotriene biosynthesis in health and disease. Biochim Biophys Acta. 2015;1851(4):331-339.
[23] Rizo J, S?dhof TC. C2-domains, structure and function of a universal Ca2+-binding domain. J Biol Chem. 1998;273(26):15879-82.
[24] Kulkarni S, Das S, Funk CD, Murray D, Cho W. Molecular basis of the specific subcellular localization of the C2-like domain of 5-lipoxygenase. J Biol Chem. 2002;277(15):13167-74.
[25] Pande AH, Qin S, Tatulian SA. Membrane fluidity is a key modulator of membrane binding, insertion, and activity of 5-lipoxygenase. Biophys J. 2005;88(6):4084-94.
[26] Walther M, Wiesner R, Kuhn H. Investigations into calcium-dependent membrane association of 15-lipoxygenase-1. Mechanistic roles of surface-exposed hydrophobic amino acids and calcium. J Biol Chem. 2004;279(5):3717-25.
[27] Butovich IA, Parshikova TV, Babenko VM, Livarchuk LV, Kharchenko OV, Kukhar VP. Regulatory role of phospholipids in the oxidation of linoleic acid by 5-lipoxygenase. Biol Membrane. 1992; 9(6): 611–6.
[28] Butovich IA, Kharchenko OV, Babenko VM. On the interfacial phenomena in lipoxygenase catalysis. Adv Prostaglandin Thromboxane Leukot Res. 1995;23:159-61.
[29] Began G, Sudharshan E, Appu Rao AG. Change in the positional specificity of lipoxygenase 1 due to insertion of fatty acids into phosphatidylcholine deoxycholate mixed micelles. Biochemistry. 1999;38(42):13920-7.
[30] Rouzer CA, Samuelsson B. On the nature of the 5-lipoxygenase reaction in human leukocytes: enzyme purification and requirement for multiple stimulatory factors. Proc Natl Acad Sci U S A. 1985;82(18):6040-4.
[31] Sud'ina GF, Brock TG, Pushkareva MA, Galkina SI, Turutin DV, Peters-Golden M, Ullrich V. Sulphatides trigger polymorphonuclear granulocyte spreading on collagen-coated surfaces and inhibit subsequent activation of 5-lipoxygenase. Biochem J. 2001;359(Pt 3):621-9.
[32] H?rnig C, Albert D, Fischer L, H?rnig M, R?dmark O, Steinhilber D, Werz O. 1-Oleoyl-2-acetylglycerol stimulates 5-lipoxygenase activity via a putative (phospho)lipid binding site within the N-terminal C2-like domain. J Biol Chem. 2005;280(29):26913-21.
[33] Aleksandrov DA, Zagryagskaya AN, Pushkareva MA, Bachschmid M, Peters-Golden M, Werz O, Steinhilber D, Sud'ina GF. Cholesterol and its anionic derivatives inhibit 5-lipoxygenase activation in polymorphonuclear leukocytes and MonoMac6 cells. FEBS J. 2006;273(3):548-57.
[34] Flamand N, Lefebvre J, Surette ME, Picard S, Borgeat P. Arachidonic acid regulates the translocation of 5-lipoxygenase to the nuclear membranes in human neutrophils. J Biol Chem. 2006;281(1):129-36.
[35] R?dmark O, Samuelsson B. Regulation of 5-lipoxygenase enzyme activity. Biochem Biophys Res Commun. 2005;338(1):102-10.
[36] Awwad K, Steinbrink SD, Fr?mel T, Lill N, Isaak J, H?fner AK, Roos J, Hofmann B, Heide H, Geisslinger G, Steinhilber D, Freeman BA, Maier TJ, Fleming I. Electrophilic fatty acid species inhibit 5-lipoxygenase and attenuate sepsis-induced pulmonary inflammation. Antioxid Redox Signal. 2014;20(17):2667-80.
[37] Riendeau D, Falgueyret JP, Nathaniel DJ, Rokach J, Ueda N, Yamamoto S. Sensitivity of immunoaffinity-purified porcine 5-lipoxygenase to inhibitors and activating lipid hydroperoxides. Biochem Pharmacol. 1989;38(14):2313-21.
[38] Rouzer CA, Samuelsson B. The importance of hydroperoxide activation for the detection and assay of mammalian 5-lipoxygenase. FEBS Lett. 1986;204(2):293-6.
[39] Wecksler AT, Garcia NK, Holman TR. Substrate specificity effects of lipoxygenase products and inhibitors on soybean lipoxygenase-1. Bioorg Med Chem. 2009;17(18):6534-9.
[40] Kilty I, Logan A, Vickers PJ. Differential characteristics of human 15-lipoxygenase isozymes and a novel splice variant of 15S-lipoxygenase. Eur J Biochem. 1999;266(1):83-93.
[41] Wecksler AT, Kenyon V, Garcia NK, Deschamps JD, van der Donk WA, Holman TR. Kinetic and structural investigations of the allosteric site in human epithelial 15-lipoxygenase-2. Biochemistry. 2009;48(36):8721-30.
[42] Armstrong MM, Diaz G, Kenyon V, Holman TR. Inhibitory and mechanistic investigations of oxo-lipids with human lipoxygenase isozymes. Bioorg Med Chem. 2014;22(15):4293-7.
[43] Mogul R, Johansen E, Holman TR. Oleyl sulfate reveals allosteric inhibition of soybean lipoxygenase-1 and human 15-lipoxygenase. Biochemistry. 2000;39(16):4801-7.
[44] Wecksler AT, Kenyon V, Deschamps JD, Holman TR. Substrate specificity changes for human reticulocyte and epithelial 15-lipoxygenases reveal allosteric product regulation. Biochemistry. 2008;47(28):7364-75.
[45] Ivanov I, Shang W, Toledo L, Masgrau L, Svergun DI, Stehling S, G?mez H, Di Venere A, Mei G, Lluch JM, Skrzypczak-Jankun E, Gonz?lez-Lafont A, K?hn H. Ligand-induced formation of transient dimers of mammalian 12/15-lipoxygenase: a key to allosteric behavior of this class of enzymes? Proteins. 2012;80(3):703-12.
[46] Butovich IA, Kharchenko OV. [Role of phospholipids in the regulation of activity of porcine leukocyte 12-lipoxygenase]. Ukr Biokhim Zh (1999). 1999;71(1):38-43.
[47] Wecksler AT, Jacquot C, van der Donk WA, Holman TR. Mechanistic investigations of human reticulocyte 15- and platelet 12-lipoxygenases with arachidonic acid. Biochemistry. 2009;48(26):6259-67.
[48] Butovich IA, Babenko VM, Livarchuk LV, Mogilevich TV, Kukhar VP. Activation of the oxidation of linoleic acid by 5-lipoxygenase from potato tubers, induced by phosphatidic acid. Biol Membrane. 1991; 56(6): 744–7.
[49] Butovich IA, Tsys EV, Mogilevich TV, Kukhar VP. Influence of physicochemical factors on lipoxygenase oxidation of linoleic acid. Bioorg Chem. 1991; 17(9):1273–80.
[50] Butovich IA, Kharchenko OV, Bondarenko LB, Babenko VM, Livarchuk LV. Linoleyl hydroxamate as 5-lipoxygenase inhibitor. Biochemistry (Moscow). 1994; 59(6):597–600.
[51] Kharchenko OV, Cernjuk VN, Butovich IA. [Inhibitory effect of linoleyl-hydroxamic acid on the oxidation of linoleic acid by 12-lipoxygenase from porcine leukocytes]. Ukr Biokhim Zh (1999). 1999;71(1):33-7.
[52] Butovich IA, Lukyanova SM. Inhibition of lipoxygenases and cyclooxygenases by linoleyl hydroxamic acid: comparative in vitro studies. J Lipid Res. 2008;49(6):1284-94.
[53] May C, H?hne M, Gnau P, Schwennesen K, Kindl H. The N-terminal beta-barrel structure of lipid body lipoxygenase mediates its binding to liposomes and lipid bodies. Eur J Biochem. 2000;267(4):1100-9.
[54] Zhang YY, Hammarberg T, Radmark O, Samuelsson B, Ng CF, Funk CD, Loscalzo J. Analysis of a nucleotide-binding site of 5-lipoxygenase by affinity labelling: binding characteristics and amino acid sequences. Biochem J. 2000;351 Pt 3:697-707.
[55] Chen XS, Funk CD. The N-terminal "beta-barrel" domain of 5-lipoxygenase is essential for nuclear membrane translocation. J Biol Chem. 2001;276(1):811-8.
[56] Albert D, Pergola C, Koeberle A, Dodt G, Steinhilber D, Werz O. The role of diacylglyceride generation by phospholipase D and phosphatidic acid phosphatase in the activation of 5-lipoxygenase in polymorphonuclear leukocytes. J Leukoc Biol. 2008;83(4):1019-27.
[57] Boden SE, Schweizer S, Bertsche T, D?fer M, Drews G, Safayhi H. Stimulation of leukotriene synthesis in intact polymorphonuclear cells by the 5-lipoxygenase inhibitor 3-oxo-tirucallic acid. Mol Pharmacol. 2001;60(2):267-73.
[58] L?pez-Nicol?s R, L?pez-Andreo MJ, Mar?n-Vicente C, G?mez-Fern?ndez JC, Corbal?n-Garc?a S. Molecular mechanisms of PKCalpha localization and activation by arachidonic acid. The C2 domain also plays a role. J Mol Biol. 2006;357(4):1105-20.
[59] Walther M, Anton M, Wiedmann M, Fletterick R, Kuhn H. The N-terminal domain of the reticulocyte-type 15-lipoxygenase is not essential for enzymatic activity but contains determinants for membrane binding. J Biol Chem. 2002;277(30):27360-6.
[60] Butovich IA, Bridnya VP, Kukhar VP. Linoleate-hydroxamic acid: a suicide inhibitor of lipoxygenase. Biokhimia (Mosk). 1990; 55(7):1216-1221.
[61] Skaterna TD, Kopich VM, Tserniuk VM, Kharchenko OV. [Modeling of linoleyl hydroxamic acid influence on lipoxygenases in vitro]. Ukr Biokhim Zh (1999). 2009;81(6):59-69.
[62] Vovk AI, Kharchenko OV, Kharitonenko AI, Kukhar' VP, Babi? LB, Kazachkov MG, Mel'nik AK, Khil'chevski? AN. [Hydrophobic nitroxyl radicals inhibit linoleyl alcohol oxidation by 5-lipoxygenase]. Bioorg Khim. 2004;30(4):436-40.
[63] Kharytonenko HI, Skaterna TD, Mel'nyk AK, Babi? LV, Kharchenko OV. [Interaction between 5-lipoxygenase and allosteric effector--sodium dodecyl sulfate]. Ukr Biokhim Zh (1999). 2008;80(3):31-9.
[64] Kooijman EE, Chupin V, de Kruijff B, Burger KN. Modulation of membrane curvature by phosphatidic acid and lysophosphatidic acid. Traffic. 2003;4(3):162-74.
[65] Joshi N, Hoobler EK, Perry S, Diaz G, Fox B, Holman TR. Kinetic and structural investigations into the allosteric and pH effect on the substrate specificity of human epithelial 15-lipoxygenase-2. Biochemistry. 2013;52(45):8026-35.
[66] Skaterna TD, Kharytonenko HI, Kharchenko OV. [Thermoinactivation of potato 5-lipoxygenase and effect of phosphatidic acid on activation energy of denaturation]. Ukr Biokhim Zh (1999). 2010;82(2):22-8.
[67] Butovich IA, Soloshonok VA, Solodenko VA, Kukhar' VP. [Activation of 5-lipoxygenase by lipophilic n-alkyl-containing acids--an allosteric process]. Bioorg Khim. 1990;16(2):270-1.
[68] Sailer ER, Schweizer S, Boden SE, Ammon HP, Safayhi H. Characterization of an acetyl-11-keto-beta-boswellic acid and arachidonate-binding regulatory site of 5-lipoxygenase using photoaffinity labeling. Eur J Biochem. 1998;256(2):364-8.
[69] Kharchenko OV, Kulinichenko HI, Butovych IA. [Kinetic mechanisms of linoleic acid oxidation by 5-lipoxygenase from Solanum tuberosum L]. Ukr Biokhim Zh (1999). 1999;71(4):40-4.
[70] Ruddat VC, Whitman S, Holman TR, Bernasconi CF. Stopped-flow kinetic investigations of the activation of soybean lipoxygenase-1 and the influence of inhibitors on the allosteric site. Biochemistry. 2003;42(14):4172-8.
[71] Butovich IA, Soloshonok VA, Kukhar VP. The unusual action of (R,S)-2-hydroxy-2-trifluoromethyl-trans-n-octadec-4-enoic acid on 5-lipoxygenase from potato tubers. Eur J Biochem. 1991;199(1):153-5.
[72] Whitman S, Gezginci M, Timmermann BN, Holman TR. Structure-activity relationship studies of nordihydroguaiaretic acid inhibitors toward soybean, 12-human, and 15-human lipoxygenase. J Med Chem. 2002;45(12):2659-61.
[73] Kharitonenko GI, Kharchenko OV. Phosphatidylcholine and phosphatidylinositol are allosteric regulators of 5-lipoxygenase from potato tubers. Biopolym Cell. 2008; 24(3):254–9.
[74] Skaterna TD, Kharchenko OV. [Effect of phosphatidic acid on the reaction of linoleic acid oxidation by 5-lipooxygenase from potatoes]. Ukr Biokhim Zh (1999). 2008;80(3):21-30.
[75] H?fner AK, Cernescu M, Hofmann B, Ermisch M, H?rnig M, Metzner J, Schneider G, Brutschy B, Steinhilber D. Dimerization of human 5-lipoxygenase. Biol Chem. 2011;392(12):1097-111.
[76] Shang W, Ivanov I, Svergun DI, Borbulevych OY, Aleem AM, Stehling S, Jankun J, K?hn H, Skrzypczak-Jankun E. Probing dimerization and structural flexibility of mammalian lipoxygenases by small-angle X-ray scattering. J Mol Biol. 2011;409(4):654-68.
[77] Parker CW, Aykent S. Calcium stimulation of the 5-lipoxygenase from RBL-1 cells. Biochem Biophys Res Commun. 1982;109(3):1011-6.