Farmaceutické aspekty živočíšnej lipoxygenázy
Authors:
Marek Obložinský; Lýdia Bezáková; Renáta Kollárová
Authors‘ workplace:
Farmaceutická fakulta Univerzity Komenského v Bratislave, Katedra bunkovej a molekulárnej biológie liečiv
Published in:
Čes. slov. Farm., 2011; 60, 116-124
Category:
Review Articles
Overview
Lipoxygenases (LOX, plant LOX [EC 1.13.11.12], linoleate: oxygen oxidoreductase, animal LOXs [5-LOX, EC 1.13.11.34; 8-LOX, EC 1.13.11.40; 12-LOX, EC 1.13.11.31; 15-LOX, EC 1.13.11.33], arachidonate: oxygen oxidoreductase) belong to the family of structurally related dioxygenases containing non-heme and non-sulfide iron in the active site. LOX catalyzes the regiospecific and stereospecific insertion of molecular oxygen into the molecule of unsaturated fatty acid with the (1Z,4Z)-penta-1,4-diene structural unit in its aliphatic chain. The result of this reaction is the production of conjugated optically active (S)- or (R)-hydroperoxides of polyunsaturated fatty acids. The occurrence of LOX was determined in plants, in animals, and also in lower organisms such as mushrooms, corals and bacteria. The dominant substrate of animal LOX is arachidonic acid which is released from membrane phospholipids by phospholipase A2 or enters the cell from the extracellular space. Products of the arachidonic acid cascade can play an important role in the pathogenesis of different diseases such as asthma bronchiale, psoriasis and inflammatory diseases, cancer diseases, atherosclerosis, diabetes mellitus and renal diseases.
Key words:
lipoxygenase – isoenzyme – inhibition – pathogenesis of different diseases
Sources
1. Shibata, D., Axelrod, B.: Plant lipoxygenases. J. Lipid Mediat. Cell Signal. 1995; 12, 213–228.
2. Brash, A. R.: Lipoxygenases: occurence, functions, catalysis, and acquisition of of substrate. J. Biol. Chem. 1999; 274, 23479–23682.
3. Andreou, A., Feussner, I.: Lipoxygenases – structure and reaction mechanism. Phytochemistry 2009; 70, 1504–1510.
4. Veldink, G. A., Hilbers, M. P., Nieuwenhuizen, W. F.: Plant lipoxygenase: structure and mechanism. In: Rowley, A.F., Kühn, H., Schewe, T. eds. Eicosanoid and related compounds in plants and animals, London, Portland Press, 1998.
5. Ueda, N., Suzuki, H., Yamamoto, S.: Mammalian lipoxygenases. Structure, functions and evolutionary aspects. In: Rowley, A. F., Kühn, H., Schewe, T. eds. Eicosanoid and related compounds in plants and animals. London: Portland Press, 1998, 47–48.
6. Bisakowski, B., Perraud, X., Kermasha, S.: Characterization of hydroperoxides and carbonyl compounds obtained by lipoxygenase extracts of selected microorganisms. Biosci. Biotechnol. Biochem. 1997; 61, 1262–1269.
7. Brash, A. R., Boeglin, W. E., Chang, M. S., Shieh, B. H.: Purification and molecular cloning of an 8R-lipoxygenase from the coral Plexaura homomalla reveal the related primary structures of R- and S-lipoxygenases. J. Biol. Chem. 1996; 271, 20949–20957.
8. Porta, H., Rocha-Sosa, M.: Lipoxygenase in bacteria: a horizontal transfer event? Microbiology 2001; 147, 3199–3200.
9. Tapiero, H., Ba, G. N., Couvreur, P., Tew, K. D.: Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies. Biomed. Pharmacother. 2002; 56, 215–222.
10. van Leyen, K., Duvoisin, R. M., Engelhardt, H., Wiedmann, M.: A function for lipoxygenase in programmed organelle degradation. Nature 1998; 395, 392–395.
11. Hill, E. M., Eling, T. E., Nettesheim, P.: Changes in expression of 15-lipoxygenases and prostaglandin H-synthase during differentiation of human tracheobronchial epithelial cells. Am. J. Respir. Cell Mol. Biol. 1998; 18, 662–669.
12. Chavis, C., Vachier, I., Bousquet, J., Godard, P., Chanez, P.: Generation of eicosanoid from 15(S)-hydroxyeicosatetraenoic acid in blood monocytes from steroid-dependent asthmatic patients. Biochem. Pharmacol. 1998; 56, 535–541.
13. Salari, H., Chan-Yeung, M.: Release of 15- hydroxyeicosatetraenoic acid (15-HETE) and prostaglandin E2 (PGE2) by cultured human bronchial epithelial cells. Am. J. Respir. Cell Mol. Biol. 1989; 1, 245–250.
14. Hill, E. M., Eling, T. E., Nettesheim, P.: Differentiation dependency of eicosanoid enzyme expression in human tracheobronchial cells. Toxicol. Lett. 1998; 96, 239–244.
15. Conrad, D. J., Lu, M.: Regulation of human 12/15-lipoxygenase by Stat6-dependent transcription. Am. J. Respir. Cell Mol. Biol. 2000; 22, 226–234.
16. Moore, P. E., Lahiri, P., Laporte, J. D., Church, T., Panettieri Jr., R. A., Shore, S. A.: Selected contribution: synergism between TNF-alpha and IL-1b in airway smooth muscle cells: implications for b-adrenergic responsiveness. J. Appl. Physiol. 2001; 91, 1467–1474.
17. Campbell, A. M., Chanez, P., Vignola, A. M., Bousquet, J.: Functional characteristics of bronchial epithelium obtained by brushing from asthmatic and normal subjects. Am. Rev. Respir. Dis. 1993; 147, 529–534.
18. Levy, B. D., Romano, M., Chapman, M. A., Reilly, J. J.: Human alveolar macrophages have 15-lipoxygenase and generate 15(S)-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid and lipoxins. J. Clin. Invest. 1993; 92, 523–531.
19. Kasahara, Y., Tuder, R. M., Cool, C. D., Voelkel, N. F.: Expression of 15-lipoxygenase and evidence for apoptosis in the lungs from patients with COPD. Chest 2000; 117, 260.
20. Zhu, J., Kilty, I., Granger, H., Gamble, E., Qiu, Y.S., Hattotuwa, K., Elston, W., Liu, W.L., Oliva, A., Pauwels, R.A., Kips, J.C., De Rose, V., Barnes, N., Yeadon, M., Jenkinson, S., Jeffery, P.K.: Gene expression and immunolocalisation of 15-lipoxygenase isozymes in the airway mucosa of smokers with chronic bronchitis. Am. J. Respir. Cell Mol. Biol. 2002; 27, 666–667.
21. Baer, A. N., Costello, P. B., Green, F. A.: Stereospecifity of the products of the fatty acids oxygenases derived from psoriatic scales. J. Lipid Res. 1991; 32, 341–347.
22. Boeglin, W. E., Kim, R. B., Brash, A. R.: A 12R-lipoxygenase in human skin: Mechanistic evidence, molecular cloning, and expression. Biochemistry 1998; 95, 6744–6749.
23. Jobard, F., Lefevre, C., Karaduman, A., Blanchet-Bardon, C., Emre, S., Weissenbach, J., Ozgüc, M., Lathrop, M., PrudęHomme, J. F., Fischer, J.: Lipoxygenase-3 (ALOXE3) and 12(R)-lipoxygenase (ALOX12B) are mutated in non-bullous congenital ichthyosiform erythroderma (NCIE) linked to chromosome 17p13.1. Hum. Mol. Genet. 2002; 11, 107–113.
24. Donoiwitz, M.: Arachidonic acid metabolites and their role in inflammatory bowel disease. Gastroenterology 1985; 88, 580–587.
25. Zijlstra, F. J., van Dijk, A. P., Garrelds, I. M., Ouwendijk, R. J. T., Wilson, J. H. P.: Species differences in the pattern of eicosanoids produced by inflamed and non-inflamed tissue. Inflamm. Res. 1991; 36, 73–75.
26. Liagre, B., Vergne, P., Rigaud, M., Beneytout, J. L.: Arachidonate 15-lipoxygenase of reticulocyte-type in human rheumatoid arthritis type B synoviocytes and modulation of its activity by proinflammatory cytokines. J. Rheumatol. 1999; 26, 1044–1051.
27. Jankum, J., Aleem, A.M., Malgorzewicz, S., Szkunlarek, M.: Synthetic curcuminoids modulate the arachidonic acid metabolism of human platelet 12‑lipoxygenase and reduce sprout formation of human endothelial cells. Mol. Cancer Ther. 2006; 5, 1371–1382.
28. Honn, K. V., Tang, D. G., Gao, X., Butovich, I. A., Liu, B., Timar, J., Hagmann, W.: 12-lipoxygenases and 12(S)-HETE: role in cancer metastasis. Cancer Metastasis Rev. 1994; 13, 365–369.
29. Nie, D., Che, M., Grignon, D., Tang, K., Honn, K. V.: Role of eicosanoids in prostate cancer progression. Cancer Metastasis Rev. 2001; 20, 195–206.
30. Ikawa, H., Kamitani, H., Calvo, B. F., Foley, J. F., Eling, T. E.: Expression of 15-lipoxygenase in human colorectal cancer. Cancer Res. 1999; 59, 360–366.
31. Kamitani, H., Geller, M., Eling, T. E.: Expression of 15-lipoxygenase by human colorectal carcinoma Caco-2 cells during apoptosis and cell differentiation. J. Biol. Chem. 1998; 273, 21569–21577.
32. Kamitani, H., Eling, T. E., Kameda, H., Kelavkar, U. K.: A GATA binding site is involved in the regulation of 15-lipoxygenase expression in human colorectal carcinoma cell line, caco-2. FEBS Lett. 2000; 467, 341–347.
33. Li, N., Sood, S., Wang, S., Fang, M.: Overexpression of 5-lipoxygenase and cyclooxygenase 2 in hamster and human oral cancer and chemopreventive effects of zileuton and celecoxib. Clin. Cancer Res. 2005; 11, 2089–2096.
34. RĆdmark, O.: 5-lipoxygenase-derived leukotrienes, mediators also of atherosclerotic inflammation. Arterioscler. Thromb. Vasc. Biol. 2003; 23, 1140–1142.
35. Melissa, E., Hatley, S.S., Kelly, B., Reilly, D.T., Hedrick, C.C.: Increased production of 12/15 lipoxygenase eicosanoids accelerates monocyte/endothelial interactions in diabetic db/db mice. J. Biol. Chem. 2003; 28, 25369–25375.
36. Mehrabian, M., Allayee, H., Wong, J., Shi, W., Wang, X. P., Shaposhnik, Z., Funk, C. D., Lusis, A. J.: Identification of 5-lipoxygenase as a major gene contributing to atherosclerosis. Circ. Res. 2002; 91, 120–126.
37. Spanbroek, R., Gräbner, R., Lötzer, K., Hildner, M., Urbach, A., Rühling, K., Moos, M. P. W., Kaiser, B., Cohnert, T. U., Wahlers, T., Zieske, A., Plenz, G., Robenek, H., Salbach, P., Kühn, H., RĆdmark, O., Samuelsson, B., Habenicht, A. J. R.: Expanding expression of the 5-lipoxygenase pathway within the arterial wall during human atherogenesis. Proc. Natl. Acad. Sci. USA 2002; 100, 1238–1243.
38. Patricia, M. K., Kim, J. A., Harper, C. M., Shih, P. T.: Lipoxygenase products increase monocyte adhesion to human aortic endothelial cells. Arterioscler. Thromb. Vasc. Biol. 1999; 19, 2615–2622.
39. Eizirik, D. L., Mandrup-Poulsen, T.: A choice of death – the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia 2001; 44, 2115–2133.
40. Bleich, D., Chen, S., Gu, J. L., Thomas, L., Scott, S., Gonzales, N., Natarajan, R., Nadler, J. L.: Interleukin-1 beta regulates the expression of a leukocyte type of 12-lipoxygenase in rat islets and RIN m5F cells. Endocrinology 1995; 136, 5736–5744.
41. Ma, Z., Ramanadham, S., Corbett, J. A., Bohrer, A., Gross, R. W., McDaniel, M. L., Turk, J.: Interleukin-1 enhances pancreatic islet arachidonic acid 12-lipoxygenase product generation by increasing substrate availability through a nitric oxide-dependent mechanism. J. Biol. Chem. 1996, 271, 1029–1042.
42. Bleich, D., Chen, S. Y., Zipser, B., Sun, D. X., Funk, C. D., Nadler, J.: Resistance to type 1 diabetes induction in 12-lipoxygenase knockout mice. J. Clin. Invest. 1999; 103, 1431–1436.
43. Antonipillai, I., Nadler, J., Vu, E. J., Bughi, S., Natarajan, R., Horton, R.: A 12-lipoxygenase product, 12-hydroxyeicosatetraenoic acid, is increased in diabetics with incipient and early renal disease. J. Clin. Endocrinol. Metab. 1996; 81, 1940–1945.
44. Pace-Asciak, C. R., Demin, P. M., Estrada, M., Liu, G.: Hepoxilins raise circulating insulin levels in vivo. FEBS Lett. 1999; 461, 165–168.
45. Falck, J. R., Manna, S., Moltz, J., Chacos, N., Capdevila, J.: Epoxyeicosatrienoic acids stimulate glucagon and insulin release from isolated rat pancreatic islets. Biochem. Biophys. Res. Commun. 1983; 114, 743–749.
46. Noiri, E., Yokomizo, T., Nakao, A., Izumi, T., Fujita, T., Kimura, S., Shimizu, T.: An in vivo approach showing the chemotactic activity of leukotriene B4 in acute renal ischemic-reperfusion injury. Proc. Natl. Acad. Sci. USA 2000; 97, 823–828.
47. Rabb, H., OęMeara, Y. M., Maderna, P., Coleman, P., Brady, H. R.: Leukocytes, cell adhesion molecules and ischemic acute renal failure. Kidney Int. 1997; 51, 1463–1468.
48. Rifai, A., Sakai, H., Yagame, M.: Expression of 5‑lipoxygenase and 5-lipoxygenase activation protein in glomerulonephritis. Kidney Int. 1993; 43, 95–99.
49. Henderson, W. R.: Products of 12- and 15-lipoxygenase. In: Henson, P.M., Murphy, R.C. eds. Mediators of the inflammatory process, Handbook of inflammation, Elsevier, Amsterdam, 1989.
50. Liaw, Y. W., Liu, Y. W., Chen, B. K., Chang, W. Ch.: Introduction of 12-LOX exspression by phorbol 12-myristate 13-acetate in human epidermoid carcinoma A431 cell. Bioch. Biophys. Acta 1998; 1389, 23–33.
51. Bors, W., Heller, W., Michel, C., Saran, M.: Flavonoids as antioxidants: Determination of radical-scavenging efficiencies. Metods Enzymol. 1990; 186, 343–345.
52. van Acker, S. A., Koymans, L. M., Bast, A.: Molecular pharmacology of vitamin E: Structural aspects of antioxidant activity. Free Radic. Biol. Med. 1993; 15, 311–328.
53. Sun, A. Y., Simonyi, A., Sun, G. Y.: The „French paradox“ and beyond: neuroprotective effects of polyphenols. Free Radic. Biol. Med. 2002; 32, 314–318.
54. Renaud, S., de Lorgeril, M.: Wine, alcohol, platelets and the french paradox for coronary heart disease. Lancet 1992; 339, 1523–1526.
55. Soleas, G. J., Diamandis, E. P., Goldberg, D. M.: Wine as a biological fluid: history, production, and role in disease prevention. J. Clin. Lab. Anal. 1997; 11, 287–313.
56. Bertolini, A., Leone, S., Ottani, A.: Dual acting anti-inflammatory drugs. Curr. Top. Med. Chem. 2007; 7, 265–275.
57. Young, R. N.: Inhibitors of 5-lipoxygenase: a therapeutic potential yet to be fully realized? Eur. J. Med. Chem. 1999; 34, 671–685.
58. Schewe, T.: Molecular actions of ebselen – an antiinflammatory antioxidant. Gen. Pharmacol. 1995; 26, 1153–1169.
59. Gao, J. X., Issekutz, A. C.: The effect of ebselen on polymorphonuclear leukocyte and lymphocyte migration to inflammatory reactions in rats. J. Immunopharmacol. 1993; 25, 239–251.
60. Takasago, T., Peters, E. E., Graham, D. I., Masayasu, H., Macrae, I. M.: Neuroprotective efficacy of ebselen, an antioxidant with anti-inflammatory actions, in rodent model of permanent middle cerebral artery occlusion. Br. J. Pharmacol. 1997; 122, 1251–1256.
61. Schewe, C., Schewe, T., Wendel, A.: Strong inhibition of mammalian lipoxygenases by the antiinflammatory seleno-organic compound ebselen in the absence of glutathione. Biochem. Pharmacol. 1994; 48, 65–74.
62. Fischer, S. M., Klein, R. D.: Lipoxygenases as targets for cancer prevention. In: Kelloff, G. J., Hawk, E. T., Sigman, C. C. eds. Cancer chemoprevention: Promising cancer chemopreventive agents, Humana Press, New Jersey, 2004.
63. Chauret, N., Li, C., Ducharme, Y., Trimble, L. A., Yergey, J. A., Ramachandran, C., Nicoll-Griffith, D. A.: In vitro and in vivo biotransformations of the naphthalenic lignan lactone 5-lipoxygenase inhibitor, L‑702,539. Drug Metabol. Dispos. 1995; 23, 65–71.
64. Funk, C. D.: Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 2001; 294, 1871–1875.
65. Cao, Y., Prescott, S. M.: Many actions of cyclooxygenase-2 in cellular dynamics and in cancer. J. Cell Physiol. 2002; 190, 279–286.
66. Datta, K., Biswal, S. S., Kehrer, J. P.: The 5-lipoxygenase-activating protein (FLAP) inhibitor, MK886, induces apoptosis independently of FLAP. Biochem. J. 1999; 340, 371–375.
67. Avis, I., Hong, S. H., Martinez, A., Moody, T., Choi, Y. H., Trepel, J., Das, R., Jett, M., Mulshine, J. L.: Five-lipoxygenase inhibitors can mediate apoptosis in human breast cancer cell lines through complex eicosanoid interactions. Faseb J. 2001; 15, 2007–2009.
68. Tang, D. G., La, E., Kern, J., Kehrer, J. P.: Fatty acid oxidation and signaling in apoptosis. Biol. Chem. 2002; 383, 425–442.
69. Datta, K., Biswal, S. S., Xu, J., Towndrow, K. M., Feng, X., Kehrer, J. P.: The 5-lipoxygenase-activating protein (FLAP) inhibitor, MK886, induces apoptosis independently of FLAP. J. Biol. Chem. 1998; 273, 28163–28169.
70. Tong, Z., Wu, X., Kehrer, J. P.: Increased expression of the lipocalin 24p3 as an apoptotic mechanism for MK886. Biochem. J. 2003; 372, 203–210.
71. Hamilton, A. L., Watson, R. M., Wyile, G., OęByrne, P. M.: Attenuation of early and late phase allergen-induced bronchoconstriction in asthmatic subjects by a 5-lipoxygenase activating protein antagonist, BAYx 1005. Thorax 1997; 52, 348–354.
72. Gambaro, G.: Strategies to safely interfere with prostanoid activity while avoiding adverse renal effects: could COX-2 and COX-LOX dual inhibition be the answer? Nephrol. Dial. Transplant. 2002; 19, 1159–1116.
73. Sala, A., Zarini, S., Bolla, M.: Leukotrienes: lipid bioeffectors of inflammatory reactions. Biochemistry (Mosc.) 1998; 63, 84–92.
74. Martel-Pelletier, J., Lajeunesse, D., Reboul, P., Pelletier, J. P.: Therapeutic role of dual inhibitors of 5-LOX and COX, selective and non-selective nonsteroidal anti-inflammatory drugs. Ann. Rheum. Dis. 2003; 62, 501–509.
75. Serhan, C. N., Levy, B. D., Clish, C. B., Gronert, K., Chiang, N.: Lipoxins, aspirin-triggered 15-epi-lipoxin stable analogs and their receptors in antiinflammation: a window for therapeutic opportunity. Ernst Schering Res. Found. Workshop 2000; 31, 143–185.
76. Leone, S., Ottani, A., Bertolini, A.: Dual acting anti-inflammatory drugs. Curr. Top. Med. Chem. 2007; 7, 265–275.
77. Laufer, S.: Discovery and development of ML3000. Inflammopharmacology 2001; 9, 101–112.
78. Fiebich, B. L., Hofer, T. J., Lieb, K., Huell, M., Butcher, R. D., Schumann, G., Schulze-Osthoff, K., Bauer, J.: The non-steroidal antiinflamatory drug tepoxalin inhibits interleukin-6 and alpha1-anti-chymotrypsin synthesis in astrocytes by preventing degradation of IkB-alpha. Neuropharmacol. 1999; 38, 1325–1333.
79. Kramer, B. C., Yabut, J. A., Cheong, J., Jnobaptiste, R., Robakis, T., Olanow, C. W., Mytilineou, C.: Toxicity of glutathione depletion in mesencephalic cultures: a role for arachidonic acid and its lipoxygenase metabolites. Eur. J. Neurosci. 2004; 19, 280–286.
80. de Gatetano, G., Donati, M. B., Cerletti, C.: Prevention of thrombosis and vascular inflamation: benefits and limitations of selective or combined COX-1, COX-2 and 5-LOX inhibitors. Trends Pharmacol. Sci. 2003; 24, 245–252.
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