Бесплатный автореферат и диссертация по биологии на тему

Исследование антиоксидантных систем эпителиальных тканей млекопитающих

ВАК РФ 03.00.02, Биофизика

Заключение Диссертация по теме "Биофизика", Кравченко, Ирина Николаевна

7.ВЫВОДЫ

1. Основным антиоксидантом в трахее крысы является 1-Cys пероксиредоксин, вклад которого в нейтрализацию активных форм кислорода составляет 70%.

2. В результате кислородного ожога верхних дыхательных путей крысы резко снижается активность супероксиддисмутазы, каталазы и глутатионпероксидазы и повышается уровень 1-Cys пероксиредоксина в эпителии трахеи. Через двое суток наблюдается резкое повышение активности всех перечисленных антиоксидантов.

3. Разработана экспериментальная модель поражения верхних дыхательных путей крысы парами соляной кислоты (химический ожог).

4. При химическом ожоге верхних дыхательных путей крысы парами соляной кислоты погибают в основном реснитчатые клетки; массовая гибель клеток наблюдается через сутки после ожога.

5. Химический ожог верхних дыхательных путей крысы сопровождается резким повышением активности нейтрофилов в эпителии трахеи. При этом снижается активность каталазы и глутатионпероксидазы и резко увеличивается уровень 1-Cys пероксиредоксина. Через сутки наблюдается восстановление активности указанных антиоксидантов.

6. Аппликация 1-Cys пероксиредоксина в трахею крысы в течение первых трех часов после химического ожога существенно защищает эпителий трахеи от поражения. В результате аппликации пероксиредоксина в течение нескольких суток в уже поврежденную трахею крысы наблюдается восстанавливающий эффект данного белка на поврежденные клетки эпителия.

6. ЗАКЛЮЧЕНИЕ

Согласно полученным результатам, 28 кДа 1-Cys пероксиредоксин в трахее и бронхах крысы является основным антиоксидантом. Поскольку наибольшее его содержание обнаружено в эпителиальных тканях, контактирующих с атмосферой, это позволяет предположить, что 1-Cys пероксиредоксин вносит существенный вклад в нейтрализацию активных форм кислорода, защищая таким образом макромолекулы и клеточные органеллы от повреждения. Повреждение эпителия трахеи и бронхов крысы, вызванное в наших экспериментах кислородным и химическим ожогами, вызывает увеличение синтеза этого белка-антиоксиданта, что также свидетельствует о его защитной роли.

Разработанная нами модель химического ожога верхних дыхательных путей крысы позволяет изучать динамику экспрессии антиоксидантов, а также исследовать активность нейтрофилов в трахее. В работе показано, что эпителий трахеи крысы, пораженный в результате химического ожога, может быть восстановлен с помощью аппликации пероксиредоксина. Показано также свойство данного белка-антиоксиданта защищать эпителий трахеи от поражающего действия паров соляной кислоты.

Полученные нами результаты могут существенно изменить современные представления об антиоксидантных системах эпителиальных тканей, в частности, эпителия органов дыхания. Данные, представленные в настоящей работе, открывают возможности использования 1-Cys пероксиредоксина для диагностики и лечения различных заболеваний органов дыхания. Уровень экспрессии пероксиредоксина может свидетельствовать о степени развития патологических процессов в тканях и органах, что важно для диагностики, а лекарственные препараты, в состав которых будет входить 1-Cys пероксиредоксин, могут оказаться очень эффективными при лечении таких патологий.

Библиография Диссертация по биологии, кандидата биологических наук, Кравченко, Ирина Николаевна, Пущино

1. Андреева С.Г, Меркулова М.И, Шуваева Т.М, Новосёлов В.И, Пешенко И.В, Новосёлов С.В, Фесенко Е.Е, Липкин В.М. Структурные исследования секреторного 28-кДа белка из обонятельного эпителия крысы. 1998 Биоорганическая химия 24 (11):825-830.

2. Афанасьев Ю.И, Юрина Н.А. Гистология. Москва, Медицина, 1989.

3. Владимиров Ю.А. и Шерстнев М.Г. Хемилюминесценция клеток животных. 1989 Итоги науки и техники. М.: ВИНИТИ т. 24, с. 176.

4. Кравченко И.Н, Янин В.А, Бондарь А.А, Барышникова J1.M, Садовников

5. B.Б, Новосёлов В.И. Химический ожог верхних дыхательных путей крысы как модель при изучении антиоксидантных систем органов дыхания. V Овчинниковские чтения "Биоорганика 2000" Москва-Пущино, стр. 100.

6. Мотавкин П.А, Гельцер Б.И. Клиническая и экспериментальная патофизиология легких. Наука, Москва, 1998 стр.7-11.

7. Новосёлов В.И, Пешенко И.В, Евдокимов В.А, Камзалов С.С, Новосёлов

8. C.В, Николаев Ю.В, Быстрова М.Ф, Фесенко Е.Е. Свойства каталитического центра секреторного 28-кДа белка (1-Cys пероксиредоксина) из обонятельного эпителия крысы. 1998 Биофизика 43 (4):610-616.

9. Новосёлов В.И, Пешенко И.В, Новоселов С.В, Камзалов С.С, Быстрова М.Ф, Евдокимов В.А, Николаев Ю.В, Фесенко Е.Е. Протекторная активность 28 кДа 1-Cys пероксиредоксина определяется его пероксидазной активностью. 1999 Биофизика 44 (3):568-570.

10. Новосёлов В.И, Амелина С.Е, Кравченко И.Н, Новосёлов С.В, Янин В.А, Садовников В.Б, Фесенко Е.Е. Роль пероксиредоксина в антиоксидантной системе органов дыхания. 2000 Доклады Академии Наук 375 (6):831-833.

11. Пешенко И.В, Новосёлов В.И, Евдокимов В.А, Николаев Ю.В, Шуваева

12. Т.М, Липкин В.М, Фесенко Е.Е. Выделение и биохимический анализ нового секреторного 28 кДа белка из обонятельного эпителия крысы. 1996 Сенсорные системы 10: 97-109.

13. Хэм А, Кормак Д. Гистология. Москва, Мир, 1983.

14. Adams D.O, Hamilton Т.А. The cell biology of macrophage activation. 1984 Ann Rev Immunol 2:283-318.

15. Adamson I.Y.R, Hedgecock C, Bowden D.H. Epithelial cell-fibroblast interactions in lung injury and repair. 1990 Am J Pathol 137:385-392.

16. Aebi H.E. Enzymes, 1: oxidoreductases, transferases. In: Bergmeyer H., Ed. Methods of enzymatic analysis, vol.III. Pp. 273-282. Deerfield Beach, F.L.: Verlag Chemie, 1980.

17. Allen R.C. and Loose L.D. Phagocytic activation of a luminol-dependent chemiluminescence in rabbit alveolar and peritoneal macrophage. 1976 Biochem Biophys Res Commun 69:245-252.

18. Almaas R., Rootwelt Т., Oyasaeter S., Saugstad O.D. Ascorbic acid enhances hydroxyl radical formation in iron-fortified infant cereals and infant formulas. 1997 Eur JPediatr 156:488-492.

19. Alvarez M.E., Pennell R.I., Meijer P.J., Ishikawa A., Dixon R.A. and Lamb C. Reactive oxygen intermediates mediate a systemic signal network in the establishment of plant immunity. 1998 Cell 92:773-784.

20. Anderson M.T., Staal F.J.T., Gilter C., Herzenberg L.A. Separation of oxidant-initiated and redox-regulated steps in the NF-кВ signal transduction pathway. 1994 Proc Natl Acad Sci U S A 9\:\\ 527-11531.

21. Asikainen T.M., Raivio K.O., Saksela M., Kinnula V.L. Expression and developmental profile of antioxidant enzymes in human lung and liver. 1998 Am JRespir Cell Mol Biol 19:942-949.

22. Babior B.M., Kipnes R.S., Curnutte J.T. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. 1973 J Clin Invest 52:741-744.

23. Bae Y.S., Kang S.W., Seo M.S., Baines I.C., Tekle E., Chock P.B. and Rhee S.G. Epidermal growth factor (EGF)-induced generation of hydrogen peroxide: Role in EGF receptor-mediated tyrosine phosphorylation. 1997 J Biol Chem 272:217221.

24. Baeuerle P.A., and Baltimore D. NF-kappa B: ten years after. 1996 Cell 87:1320.

25. Ballinger C.A., Mendis-Handagama C., Kalmar J.R., Arnold R.R., Kinkade J.M. Changes in the localization of catalase during differentiation of neutrophilic granulocytes. 1994 Blood 83:2654-2668.

26. Barnes P.J. New concepts in the pathogenesis of bronchial hyperresponsiveness and asthma. 1989a J Allergy Clin Immunol 83:1013-1026.

27. Barnes P.J. A new approach to asthma therapy. 1989b N Engl J Med 321:15171527.

28. Barnes P.J. Reactive oxygen species and airway inflammation. 1990 Free Radic Biol Med 9:235-243.

29. Basbaum C.B. Regulation of airway secretory cells. 1986 Clinics in Chest Medicine 7 (2):231-237.

30. Basbaum C.B. and Finkbeiner W.E. Airway secretion: a cell-specific analysis. 1988 Horm. Metabol. Res. 20:661-667.

31. Bast A, Haenen G, Doelman C. Oxidants and antioxidants: state of the art. 1991 Am J Med 91:2S-13S.

32. Battistoni A, Folcarelli S, Cervoni L, et al. Role of the dimeric structure in Cu,Zn superoxide dismutase. pH-dependent, reversible denaturation of the monomeric enzyme from Escherichia coli. 1998 J Biol Chem 273:5655-5661.

33. Bauer V, Bauer F. Reactive oxygen species as mediators of tissue protection and injury. 1999 Gen Physiol Biophys 18:7-14.

34. Becker S, Soukup J.M, Gilmour M.I, Devlin R.B. Stimulation of human and rat alveolar macrophages by urban air particulates: effects on oxidant radical generation and cytokine production. 1996 Toxicol Appl Pharmacol 141:637-648.

35. Berg I, Schluter T, Gercken G. Increase of bovine alveolar macrophage superoxide anion and hydrogen peroxide release by dusts of different origin. 1996 J Toxicol Environ Health 47:465-478.

36. Bervoets K, Schlenzing J.S, Bohles H. Bilirubin in the early neonatal period. Is there a positive aspect of hyperbilirubinemia? A medical hypothesis. 1994 Fortschr. Med. 112:192-194.

37. Boat T.F, Cheng P.W, Iyer R.N, Carlson D.M, Polony I. Human respiratory tract secretions: mucus glycoproteins of nonpurulent tracheobronchial secretions, and sputum of patiens with bronchitis and cystic fibrosis. 1976 Arch Biochem Biophys 177:95-104.

38. Borzi R.M, Grigolo B, Meliconi R, Fasano L, Sturani C, Fabbri M, et al. Elevated serum superoxide dismutase levels correlate with disease severity and neutrophil degranulation in idiopathic pulmonary fibrosis. 1993 Clin Sci 85:353359.

39. Bradford M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing of protein-dye binding. 1967 Anal. Biochem. 72:248-254.

40. Brody A. Asbestos-induced lung disease. 1993 Environ Health Perspect 100:2130.

41. Buhl R. Imbalance between oxidants and antioxidants in the lungs of HIV-seropositive individuals. 1994 Chem-Biol Interact 91:147-58.

42. Burton G, Ingold K. Mechanisms of antioxidant action: preventive and chain-breaking antioxidant. In: CRC Handbook of Free Radicals and Antioxidants in Biomedicine, II (Quintanilha A, ed.). Boca Raton, FL:CRC Press, 1989, 29-43.

43. Buschfort C, Muller M.R, Seeber S, Rajewsky M.F, Thomale J. DNA excision repair profiles of normal and leukemic human lymphocytes: functional analysis at the single-cell level. 1997 Cancer Res 57:651-658.

44. Busse W.W, Horwitz R.J, Reed C.E. Asthma. Definition and pathogenesis. In: Allergy. Principles & Practice (Middleton E. Jr., Reed C.E, Ellis E.F, Adkinson N.F. Jr., Yunginger J.W, Busse W.W, editors). Mosby, St. Louis 1998 pp. 838858.

45. Camhi S.L, Lee P, Choi A.M.K. The oxidative stress response. 1995 New Horizons 3:170-182.

46. Canada A.T, Herman L.A, Young S.L. An age-related difference in hyperoxia lethality: role of lung antioxidant defense mechanisms. 1995 Am J Physiol 268 (Lung Cell Mol Physiol 12) :L539-L545.

47. Cantin A.M., North S.L, Hubbard R.C, Crystal R.G. Normal alveolar epithelial lining fluid contains high levels of glutathione. 1987 J Appl Physiol 63:152-157.

48. Cantin A.M., Fells G.A, Hubbard R.C, Crystal R.G. Antioxidant macromolecules in the epithelial lining fluid of the normal human lower respiratory tract. 1990 J Clin Invest 86:962-971.

49. Chae H.Z, Kim I.-H, Kim K. and Rhee S.G. Cloning, sequencing, and mutation of thiol-specific antioxidant gene of Saccharomyces cerevisiae. 1993 J Biol Chem 268:16815-16821.

50. Chae H.Z, Chung S.J. and Rhee S.G. Thioredoxin-dependent peroxide reductase from yeast. 1994b J Biol Chem 269:27670-27678.

51. Chae H.Z, Uhm T.B. and Rhee S.G. Dimerization of thiol-specific antioxidant and the essential role of cysteine 47. 1994c Proc Natl Acad Sci USA 91:70227026.

52. Chen F, Deng H.Y, Ding D.F, Houng D.W, Daniel L.N, Long Z.Z. Excessive production of insulin-like growth factor-1 by silicostic rat alveolar macrophages. 1994 Arch PatholMicribiol Immunol Scand 102:581-588.

53. Chen Q., Olashaw N., Wu J. Participation of reactive oxygen species in the lysophosphatidic acid-stimulated mitogen-activated protein kinase kinase activation pathway. 1995 J Biol Chem 270:28499-28502.

54. Choi H.-J., Kang S.W., Yang C.-H, Rhee S.G. and Ryu S.-E. Crystal structure of a novel human peroxidase enzyme at 2.0 angstrom resolution. 1998 Nat Struct Biol 5:400-406.

55. Chopra S., Wallace H.M. Induction of spermidine/spermine Nl-acetyltransferase in human cancer cells in response to increased production of reactive oxygen species. 1998 Biochem Pharmacol 55:1119-1123.

56. Church D.F., Pryor W.A. Free-radical chemistry of cigarette smoke and its toxicological implications. 1985 Environ Health Perspect 64:111-126.

57. Claiborne A., Miller H., Parsonage D., Ross R.P. Protein-sulfenic acid stabilization and function in enzyme catalysis and gene regulation. 1993 FASEB /7:1483-1490.

58. Clerch L.B., Massaro D. Tolerance of rats to hyperoxia-lung antioxidant enzyme gene expression. 1993 J Clin Invest 91:499-508.

59. Clyde B.L., Chang L.Y., Auten R.L., Ho Y.S., Crapo J.D. Distribution of manganese superoxide dismutase mRNA in normal and hyperoxic lung. 1993 Am JRespir Cell Mol Biol 8:530-537.

60. Cohn L.A., Kinnula V.L., Adler K.B. Antioxidant properties of guinea pig tracheal epithelial cells in vitro. 1994 Am J Physiol 266:L397-L404.

61. Cortijo J., Marti-Cabrere M., de la Asuncion J.G., Pallardo F.V., Esteras A., Bruseghini L., Vina J., Morcillo E.J. Contraction of human airways by oxidative stress protection by N-acetylcysteine. 1999 Free Radic Biol Med 27 (3-4):392-400.

62. Crapo J.D., Barry B.E., Foscue H.A., Shelburne J. Structural and biochemical changes in rat lungs occurring during exposure to lethal and adaptive doses of oxygen. 1980 Am Rev Respir Dis 122:123-143.

63. Cross C.E., Halliwell В., Allen A. Antioxidant protection: a function of tracheobronchial and gastrointestinal mucus. 1984 Lancet 1:1328-1330.

64. Cross С., Halliwell В. Biological consequences of general environmental contaminants. In: The Lung. Scientific Foundations (Crystal R., West J., eds). New York: Raven Press, 1991; 1961-1973.

65. Czene S., Tiback M., Harms-Ringdahl M. pH-dependent DNA cleavage in permeabilized human fibroblasts. 1997 Biochem 7323:337-341.

66. Daniel L.N., Mao Y., Saffiotti U. Oxidative DNA damage by crystalline silica. 1993 Free Radic Biol Med 14:463-472.

67. Davis J.M., Rosenfeld W.N., Sanders R.J., Gonenne A. Prophylactic effects of recombinant superoxide dismutase in neonatal lung injury. 1993 J Appl Physiol 74:2234-2241.

68. De Raeve H.R., Thunnissen F.B., Kaneko F.T., et al. Decreased Cu,Zn-SOD activity in asthmatic airway epithelium: correction by inhaled corticosteroid in vivo. 1997 Am J Physiol 272:148.

69. Ehrenkranz R.A., Ablow R.C., Warshaw J.B. Effect of vitamin E on the development of oxygen-induced lung injury in neonates. 1982 Ann NY Acad Sci 393:452-466.

70. Ellis H.R. and Poole L.B. Novel application of 7-chloro-4-nitrobenzo-2-oxa-l,3-diazole to identify cysteine sulfenic acid in the AhpC component of alkyl hydroperoxide reductase. 1997a Biochemistry 36:15013-15018.

71. Ellis H.R. and Poole L.B. Roles for the two cysteine residues of AhpC in catalysis of peroxide reduction by alkyl hydroperoxide reductase from Salmonella typhimurium. 1997b Biochemistry 36:13349-13356.

72. Engstrom P.C., Easterling L., Baker R.R., Matalon S. Mechanisms of extracellular hydrogen peroxide clearance by alveolar type II pneumocytes. 1990 J Appl Physiol 69:2078-2084.

73. Erzurum S.C., Danel C., Gillissen A., Chu C.S., Trapnell B.C., Crystal R.G. In vivo antioxidant gene expression in human airway epithelium of normal individuals exposed to 100% 02. 1993 J Appl Physiol 75:1256-1262.

74. Esterbauer H., Gebicki J., Puhl H., Jugens G. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. 1992 Free Radic Biol Med 13:341-390.

75. Finkel T. Oxygen radicals and signaling. 1998 Curr Opin Cell Biol 10:248-253.

76. Forman H.J, Fisher A.B. Antioxidant enzymes of rat granular pneumocytes. Constitutive levels and effect of hyperoxia. 1981 Lab Invest 45:1-6.

77. Fox R.B, Hoidal J.R, Brown D.M, Repine J.E. Pulmonary inflammation due to oxygen toxicity: involvement of chemotactic factors and polymorphonuclear leukocytes. 1981 Am Rev Respir Dis 123:521.

78. Frank S, Munz B. and Werner S. The human homologue of a bovine non-selenium glutathione peroxidase is a novel keratinocyte growth factor-regulated gene. 1997 Oncogene 14:915-921.

79. Freeman B.A, Mason R.J, Williams M.C, Crapo J.D. Antioxidant enzyme activity in alveolar type II cells after exposure of rats to hyperoxia. 1986 Exp Lung Res 10:203-222.

80. Fridovich I. Superoxide dismutases: regularities and irregularities. In: The Harvey lectures, series 79. New York: Academic Press, 1983 pp. 51-75.

81. Fridovich I. Superoxide dismutases. 1986 Adv Enzymol Relat Areas Mol Biol 58:61-97.

82. Fridovich I, Freeman B. Antioxidant defenses in the lung. 1986 Annu Rev Physiol 48:693-702.

83. Fu S, Davies M.J, Stocker R, Dean R.T. Evidence for roles of radicals in protein oxidation in advanced human atherosclerotic plaque. 1998 Biochem J 333:519-525.

84. Fulkerson W, Maclntyre N, Stamler J, Crapo J. Pathogenesis and treatment of the adult respiratory distress syndrome. 1996 Arch Intern Med 156:29-38.

85. Ghosh J, Myers C.E. Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells. 1998 Proc Natl Acad Sci 95:1318213187.

86. Gossart S, Cambon C, Orfila C, Seguelas M.-H, Lepert J.-C, Rami J, Carre P, Pipy B. Reactive oxygen intermediates as regulators of TNF-alpha production in rat lung inflammation induced by silica. 1996 J Immunol 156:1540-1548.

87. Grazioli V, Schiavo R, Casari E, et al. Antioxidant enzymatic activities and lipid peroxidation in cultured human chondrocytes from vertebral plate cartilage. 1998 FEBS Lett 431:149-153.

88. Groen H, Hamstra M, Aalbers R, van der Mark T.W, Koeter G.H, Postma D.S. Clinical evaluation of lymphocyte sub-populations and oxygen radical production in sarcoidosis and idiopathic pulmonary fibrosis. 1994 Respir Med 88:55-64.

89. Grum C.M., Ragsdale R.A., Ketai L.H., Simon R.H. Plasma xanthine oxidase activity in patients with adult respiratory distress syndrome. 1987 J Crit Care 2:223-226.

90. Halliwell B. Antioxidant defence mechanisms: from the beginning to the end (of the beginning). 1999 Free Rad Res 31:261-272.

91. Haridas V., Ni J., Meager A., Su J., Yu G.-L., Zhai Y., Kyaw H., Akama K.T., Hu J., Van Eldik L.J. and Aggarwal B.B. TRANK, a novel cytokine that activates NF-кВ and c-Jun N-terminal kinase. 1998 J Immunol 161:1-6.

92. Hecht D., Zick Y. Selective inhibition of protein tyrosine phosphatase activities by

93. H202 and vanadate in vitro. 1992 Biochem Biophys Res Comm 188:773-779.

94. Hedenborg M., Klockars M. Production of reactive oxygen metabolites induced by asbestos fibers in human polymorphonuclear leukocytes. 1987 J Clin Pathol 40:1189-1193.

95. Hinsch K.D., Tychowiecka I., Gausepohl H., Frank R., Rosenthal W., Schultz G. Tissue distribution of pr and (32-subunits of regulatory guanine nucleotide-binding proteins. 1989 Biochim Biophys Acta. 1013:60-67.

96. Ho Y.-S. Dey M.S., Crapo J.D. Antioxidant enzyme expression in rat lungs during hyperoxia. 1996 Am J Physiol 270 (Lung Cell Mol Physiol 14): L810-L818.

97. Hurst R., Bao Y., Jemth P., Mannervik В., Williamson G. Phospholipid hydroperoxide glutathione peroxidase activity of rat class Theta glutathione transferase T2-2. 1997 Biochem Soc Trans 25:S559.

98. Ichimiya S., Davis J. G., O'Rourke D. M., Katsumata M. and Greene M. I. Murine thioredoxin peroxidase delays neuronal apoptosis and is expressed in areas of the brain most susceptible to hypoxic and ischemic injury. 1997 DNA Cell Biol 16:311-321.

99. Imai H., Narashima K., Arai M., Sakamoto H., Chiba N., Nakagawa Y. Suppression of leukotriene formation in RBL-2H3 cells that overexpressed phospholipid hydroperoxide glutathione peroxidase. 1998 J Biol Chem 273:1990-1997.

100. Inan С, Kilic I, Kilinc K, Kalayci O, Kotiloglu E. The effect of high dose antenatal vitamin E on hypoxia-induced changes in newborn rats. 1995 Pediatr Res 38:685-689.

101. Ishii T, Yamada M, Sato H, Matsue M, Taketani S, Nakamura K, Sugita I, Bannai S. Cloning and characterization of a 23-kDa stress-induced mouse peritoneal macrophage protein. 1993 J Biol Chem 268:18633-18636.

102. Jackson R.M. Molecular, pharmacologic and clinical aspects of oxygen-induced lung injury. 1990 Clinics in Chest Medicine 11(1) :73-86.

103. Jacobson F.S, Morgan R.W, Christman M.F, Ames B.N. An alkyl hydroperoxide reductase from Salmonella typhimurium involved in the defense of DNA against oxidative damage. Purification and properties. 1989 J Biol Chem 264:1488-1496.

104. Jacobson M.D. Reactive oxygen species and programmed cell death. 1996 Trends Biochem Sci 21:83-86.

105. Jacquot J, Hayem A, Galabert C. Functions of proteins and lipids in airway secretions. 1992 Eur RespirJ 5:343-358.

106. Janssen Y.M.W, van Houten B, Borm P.J.A, Mossman B.T. Biology of disease. Cell and tissue responses to oxidative damage. 1993 Lab Invest 69:261274.

107. Janssen Y.M.W, Marsh J.P, Absher M.P, Gabrielson E, Borm P.J.A, Driscoll K.E, et al. Oxidant stress responses in human pleural mesothelial cells exposed to asbestos. 1994b Am JRespir Crit Care Med 149:795-802.

108. Jarjour N.N, Calhoun W.J. Enhanced production of oxygen radicals in asthma. 1994 J Lab Clin Med 123:131-136.

109. Jeffery P.K. and Li D. Airway mucosa: secretory cells, mucus and mucin genes. 1997 Eur Respir J10:1655-1662.

110. Jeh J.I, Claiborne A, Hoi W.G. Structure of the native cysteine-sulfenic acid redox center of enterococcal NADH peroxidase refined at 2.8 A resolution. 1996 Biochemistry 35:9951-9957.

111. Jenkinson S.G, Black R.D, Lawrence R.A. Glutathione concentrations in rat lung bronchoalveolar lavage fluid: effects of hyperoxia. 1988 J Lab Clin Med 112:345-351.

112. Jin D.-Y., Chae H.Z., RJiee S.G. and Jeang K.-T. Regulatory role for a novel human thioredoxin peroxidase in NF-кВ activation. 1997 J Biol Chem 272:30952-30961.

113. Jornot L., Junod A.F. Response of human endothelial cell antioxidant enzymes to hyperoxia. 1992 Am J Respir Cell Mol Biol 6:107-115.

114. Jornot L., Petersen H., Junod A. F. Hydrogen peroxide-induced DNA damage is independent of nuclear calcium but dependent on redox-active ions. 1998 BiochemJ 335:85-94.

115. Junod A.F. Oxygen free radicals and lungs. 1989 Intensive Care Med 15:S21-S23.

116. Kaliner M.A. Human nasal respiratory secretions and host defense. 1991 Am Rev Respir Dis 144:S52-S56.

117. Kamp D.W., Graceffa P., Pryor W.A., Weitzman S.A. The role of free radicals in asbestos-induced diseases. 1992 Free Radic Biol Med 12:293-315.

118. Kanazawa H., Kurihara N., Hirata K., Takeda T. The role of free radicals in airway obstruction in asthmatic patients. 1991 Chest 100:1319-1322.

119. Kang S.W., Chae H.Z., Seo M.S., Kim K., Baines I.C. and Rhee S.G. Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-a. 1998a J Biol Chem 273:6297-6302.

120. Kang S.W., Baines I.C. and Rhee S.G. Characterization of a mammalian peroxiredoxin that contains one conserved cysteine. 1998b J Biol Chem 273:6303-6311.

121. Kasprzak K.S. Possible role of oxidative damage in metal-induced carcinogenesis. 1995 Cancer Invest 13:411-430.

122. Kawai S., Takesita S., Okazaki M., Kikuno R., Kudo A. and Amann E. Cloning and characterization of OSF-3, a new member of the MER5 family, expressed in mouse osteoblastic cells. 1994 JBiochem (Tokyo) 115:641-643.

123. Keating V.M., Collins P.D., Scott D.M., Barnes P.J. Differences in interleukin-8 and tumor necrosis factor-induced sputum from patients with chronic obstructive pulmonary disease or asthma. 1996 Am J Respir Crit Care Med 153:530-534.

124. Kelly F.J. Gluthathion: in defence of the lung. 1999 Food Chem Toxicol 37 (9-10):963-966.

125. Kennedy C.H, Cueto R, Belinsky S.A, Lechner J.F, Pryor W.A. Overexpression of hMTHl mRNA: a molecular marker of oxidative stress in lung cancer cells. 1998 FEBSLett 429:17-20.

126. Keyse S, Tyrrel R. Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenate. 1989 Proc Natl Acad Sci USA 11:787-791.

127. Kim K, Kim I.H, Lee K.-Y, Rhee S.G. and Stadtman E.R. The isolation and purification of a specific "protector" protein which inhibits enzyme inactivation by a thiol/Fe(III)/02 mixed-function oxidation system. 1988 J Biol Chem 263:4704-4711.

128. Kinnula V.L, Whorton A.R, Chang L.Y, Crapo J.D. Regulation of hydrogen peroxide generation in cultured endothelial cells. 1992a Am JRespir Cell Mol Biol 6:175-182.

129. Kinnula V.L, Chang L, Everitt J.I, Crapo J.D. Oxidants and antioxidants in alveolar epithelial type II cells: in situ, freshly isolated and cultured cells. 1992b Am J Physiol 262:L69-L77.

130. Kinnula V.L, Everitt J.I, Mangum J.B, Chang L.-Y, Crapo J.D. Antioxidant defense mechanisms in cultured pleural mesothelial cells. 1992c Am J Respir Cell Mol Biol 7:95-103.

131. Kinnula V.L, Aalto K, Raivio K.O, Walles S, Linnainmaa K. Cytotoxicity of oxidants and asbestos fibers in cultured human mesothelial cells. 1994a Free Radic Biol Med 16:169-176.

132. Kinnula V.L, Yankaskas J.R, Chang L, Virtanen I, Linnala A, Crapo J.D. Primary and immortalized (BEAS 2B) human bronchial epithelial cells have significant antioxidative capacity in vitro. 1994b Am J Respir Cell Mol Biol 11:568-576.

133. Kinnula V.L, Pietarinen P, Aalto K, Virtanen I, Raivio K.O. Mitochondrial superoxide dismutase induction does not protect epithelial cells during oxidant exposure in vitro. 1995a Am J Physiol 268:L71-77.

134. Kinnula V.L, Crapo J.D, Raivio K.O. Biology of Disease. Generation and disposal of reactive oxygen metabolites in the lung. 1995b Laboratory Investigation 73 (1 ):3-19.

135. Kinsella J.P, Walsh W.F, Bose C.I. et al. Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomized controlled trial. 1999 Lancet 354:1061-1065.

136. Knoops B, Clippe A, Bogard C, Arsalane K, Wattiez R, Hermans C, Duconseille E, Falmagne P, Bernard A. Cloning and characterization of

137. АОЕВ166, a novel mammalian antioxidant enzyme of the peroxiredoxin family. 1999 J Biol Chem 274 (43):30451-30458.

138. Kowaltowski A.J, Netto L.E. and Vercesi A.E. The thiol-speciflc antioxidant enzyme prevents mitochondrial permeability transition: Evidence for the participation of reactive oxygen species in this mechanism. 1998 J Biol Chem 273:12766-12769.

139. Krieger-Brauer H.I, Kather H. Antagonistic effects of different members of the fibroblast and platelet-derived growth factor families on adipose conversion and NADPH-dependent H202 generation in 3T3 LI-cells. 1995 Biochem J 307:549556.

140. Laemmli U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. 1970 Nature 227:680-685.

141. Lamb D. and Reid L. Histochemical types of acidic glycoprotein produced by mucous cells of the thraheobronchial glands in man. 1969 J Pathol 98:213-229.

142. Lamb D. and Reid L. Histochemical and autoradiographic investigation of the serous cells of the human bronchial glands. 1970 J Pathol 100:127-138.

143. Leah R.B, Casareno D.W, Gitlin J.D. The copper chaperone CCS directly interacts with copper/zinc superoxide dismutase. 1998 J Biol Chem 273:2362523628.

144. Lee J, Spector D, Godon C, Labarre J. and Toledano M.B. A new antioxidant with alkyl hydroperoxide defense properties in yeast. 1999 J Biol Chem 274:4537-4544.

145. Leff J.A, Parsons P.E, Day C.E, Moore E.E, Moore F.A, Oppegard M.A, et al. Increased serum catalase activity in septic patiens with the adult respiratory distress syndrome. 1992 Am Rev Respir Dis 146:985-989.

146. Leone M, Cupane A, Militello V, Stroppolo M.E, Desideri A. Fourier Transform infrared analysis of the interaction of azide with the active site of oxidized and reduced bovine Cu,Zn superoxide dismutase. 1998 Biochemistry 37:4459-4464.

147. Lo Y.Y, Cruz T.F. Involvement of reactive oxygen species in cytokine and growth factor induction of c-fos expression in chondrocytes. 1995 J Biol Chem 270:11727-11730.

148. Lubec G., Widness J.A., Hayde M., Menzel D., Pollak A. Hydroxyl radical generation in oxygen-treated infants. 1997 Pediatrics 100:700-704.

149. MacMillan-Crow L.A., Crow J.P., Thompson J.A. Peroxynitrite-mediated inactivation of manganese superoxide dismutase involves nitration and oxidation of critical tyrosine residues. 1998 Biochemistry 37:1613-1622.

150. MacNee W., Rahman I. Oxidants and antioxidants as therapeutic targets in chronic obstructive pulmonary disease. 1999 Am J Respir Crit Care Med 160:S58-S65.

151. Margraf L.R., Tomashefski J.F., Bruce M.C., Dahms B.B. Morphometric analysis of the lung in bronchopulmonary dysplasia. 1991 Am Rev Respir Dis 143:391-400.

152. Marklund S.L. Extracellular superoxide dismutase in human tissues and human cell lines. 1984 J Clin Invest 74:1398-1403.

153. Martin L.D., Krunkosky T.M., et al. The role of reactive oxygen and nitrogen species in the response of airway epithelium to particulates. 1997 Environ Health Perspect Suppl 105 (5): 1301-1307.

154. Martin L.D., Krunkosky T.M., Voynow J.A., Adler K.B. The role of reactive oxygen and nitrogen species in airway epithelial gene expression. 1998 Environ Health Perspect Suppl 106 (5): 1197-1202.

155. Mates J.M., Perez-Gomes C., De Castro I.N. Antioxidant enzymes and human diseases. 1999 Clinical Biochemistry 32 (8):595-603.

156. McDonald R.J., Berger E.M., Repine J.E. Alveolar macrophage antioxidants prevent hydrogen peroxide-mediated lung damage. 1991 Am Rev Respir Dis 143:1088-1091.

157. Meier В., Radeke H.H., Selle S., Younes M., Sies H., Resch K., Habermehl G.G. Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-alpha. 1989 Biochem /263:539-545.

158. Meier В., Scherk C., Schmidt M., Parak F. pH-dependent inhibition by azide and fluoride of the iron superoxide dismutase from Propionibacterium shermanii. 1998 Biochem J 331:403-407.

159. Mills E.M., Takeda K., Yu Z.X., et al. Nerve growth factor treatment prevents the increase in superoxide produced by epidermal growth factor in PC 12 cells. 1998 J Biol Chem 273:22165-22168.

160. Miyamoto S., Schmitt M.J., Verma I.M. Qualitative changes in the subunit composition of kappa B-binding complexes during murine B-cell differentiation. 1994 Proc Natl Acad Sci USA 91:5056-5060.

161. Morrison D., Rahman I., Lannan S., MacNee W. Epithelial permeability, inflammation, and oxidant stress in the air spaces of smokers. 1999 Am J Respir Crit Care Med 159:473-479.

162. Muller J.M., Rupee R.A., Baeuerle P. A. Study of gene regulation by NF-kappa В and AP-1 in response to reactive oxygen intermediates. 1997 Methods (Orlando) 11:301-312.

163. Munz В., Frank S., Hubner G., Olsen E. and Werner S. A novel type of glutathione peroxidase: expression and regulation during wound repair. 1997 Biochem J326:579-585.

164. Nakamura H., Nakamura K., Yodoi I. Redox regulation of cellar activation. 1997 Annu Rev Immunol 15:351-369.

165. Nathanson I. and Nadel J.A. Review: movement of electrolytes and fluid across airways. 1984 Lung 162:125-137.

166. Numagami Y., Marro P.J., Mishra O.P., Delivoria Papadopoulos M. Effect of propentofylline on free-radical generation during cerebral hypoxia in the newborn piglet. 1998 Neuroscience 84:1127-1133.

167. Nyberg P., Klockars M. Measurement of reactive oxygen metabolites produced by human monocyte-derived macrophages exposed to mineral dusts. 1990 Int J Exp Pathol 71:537-544.

168. Oakley B.R., Kirsch D.R., Morris N.R. 1980 Annal. Biochem. 105:361-366.

169. Ogihara Т., Okamoto R., Kim H.-S., Nagai A., Morinobu Т., Moji H., Kamegai H., Hirano K., Ogihara H., Tamai H., Mino M. New evidence for the involvement of oxygen radicals in triggering neonatal chronic lung disease. 1996 Pediatr Res 39:117-119.

170. Ohba M., Shibanuma M., Kuroki Т., Nose K. Production of hydrogen peroxide by transforming growth factor-beta 1 and its involvement in induction of egr-1 in mouse osteoblastic cells. 1994 J Cell Biol 126:1079-1088.

171. Ono M., Kohda H., Kawaguchi Т., Ohhira M., Sekiya С., Namiki M., et al. Induction of Mn-superoxide dismutase by tumor necrosis factor, interleukin-1 and interleukin-6 in human hepatoma cells. 1992 Biochem Biophys Res Commun 182:1100-1107.

172. Oroszlan G., Sanderud J., Saugstad O.D., Lakatos L. D-penicillamine: old drug, new indication? 1992 Orv. Hetil. 133:2835-2836.

173. Oury T.D., Chang L.-Y., Marklund S.L., Day B.J., Crapo J.D. Immunocytochemical localization of extracellular superoxide dismutase in human lung. 1994 Lab Invest 70:889-898.

174. Pacht E.R., Timerman A.P., Lykens M.G., Merola A.J. Deficiency of alveolar fluid glutathione in patiens with sepsis and the adult respiratory distress syndrome. 1991 Chest 100:1397-1403.

175. Pahl H.L., Baeuerle P.A. Oxygen and the control of gene expression. 1994 Bioessays 16:497-502.

176. Palmer C., Roberts R.L., Bero C. Deferoxamine postreatment reduces ischemic brain injury in neonatal rats. 1994 Stroke 25:1039-1045.

177. Papparella A., DeLuca F.G., Oyer C.E., Pinar H., Stonestreet B.S. Ischemia-reperfusion injury in the intestines of newborn. 1997 Pediat Res 42:180-188.

178. Penn J.S., Tolman B.L., Bullard L.E. Effect of a water-soluble vitamin-analog of retinopathy of prematurity. 1997 Free Radio Biol Med 22:977-984.

179. Peshenko I.V., Novoselov V.I., Evdokimov V.A., Nikolaev Yu.V., Shuvaeva T.M., Lipkin V.M., Fesenko E.E. Novel 28-kDa secretory protein from rat olfactory epithelium. 1996 FEBS Lett 381:12-14.

180. Peterhans E. Reactive oxygen species and nitric oxide in viral diseases. 1997 Biol Trace Elem Res 56:107-116.

181. Pincemail J., Defraigne J.O., Franssen C., Bonnet P., Deby-Dupont G., Pirenne J., et al. Evidence for free radical formation during human kidney transplantation. 1993 Free Radic Biol Med 15:343-348.

182. Piquet P.F., Collart M.A., Grau G.E., Sappino A.P., Vassalli P. Requirement of tumor necrosis factor for development of silica-induced pulmonary fibrosis. 1990 Nature 344:245-247.

183. Poole L.B. and Claiborne A. The non-flavin redox center of the streptococcal NADH peroxidase. I. Thiol reactivity and redox behavior in the presence of urea. 1989a J Biol Chem 264:12322-12329.

184. Poole L.B. and Claiborne A. The non-flavin redox center of the streptococcal NADH peroxidase. II. Evidence for a stabilized cysteine-sulfenic acid. 1989b J Biol Chem 264:12330-12338.

185. Poole L.B. and Ellis H.R. Flavin-dependent alkyl hydroperoxide reductase from Salmonella typhimurium. 1. Purification and enzymatic activities of overexpressed AhpF and AhpC proteins. 1996 Biochemistry 35:56-64.

186. Poole L.B. Flavin-dependent alkyl hydroperoxide reductase from Salmonella typhimurium. 2. Cystine disulfides involved in catalysis of peroxide reduction. 1996 Biochemistry 35:65-75.

187. Prosperi M.T, Ferbus D, Karczinski I. and Goubin G. A human cDNA corresponding to a gene overexpressed during cell proliferation encodes a product sharing homology with amoebic and bacterial proteins. 1993 J Biol Chem 268:11050-11056.

188. Prosperi M.T, Ferbus D, Rouillard D. and Goubin G. The pag gene product, a physiological inhibitor of c-Abl tyrosine kinase, is overexpressed in cells entering S phase and by contact with agents inducing oxidative stress. 1998 FEBS Lett 423:39-44.

189. Puchelle E, Zahm J.M, Petit A. Spinability and transport properties of sputum in chronic bronchitis. In: Chantler N, Elder J.B, Epstein M, eds. Mucus in Health and Disease. New York, Plenum Press, 1982; pp. 397-398.

190. Radi R, Turrens J.F, Chang L.-Y, Bush K.M, Crapo J.D, Freeman B.A. Detection of catalase in rat heart mitochondria. 1991 J Biol Chem 266:2202822034.

191. Rice-Evans C.A, Diplock A.T. Current status of antioxidant therapy. 1993 Free Radical Biol Med 15:77-96.

192. Rikans L.E, Hornbrook K.R. Lipid peroxidation, antioxidant protection and aging. 1997 Biochim Biophys Acta 1362:116-127.

193. Roomans G.M, von Euler A.M., Muller R.M, Gilljam H. X-ray microanalysis of goblet cells in bronchial epithelium of patients with cystic fibrosis. 1986 J Submicrosc Cytol 18:613-615.

194. Rosenberg A.A. Inhaled nitric oxide in the premature infant with severe hypoxaemic respiratory failure: A time for caution. 1998 J Pediatr 133 (6): 720722.

195. Rosenfeld W.N, Davis J.M. Prevention of oxygen radical disease in the newborn: possible therapeutic approaches. 1998 Semin Neonatol 3:239-244.

196. Rubilloud T, Berthier R, Vincon M, Ferbus D, Goubin G. and Lawrence J.J. Early events in erythroid differentiation: accumulation of the acidic peroxiredoxin (PRP/TSA/NKEF-B). 1995 Biochem /312:699-705.

197. Ryrfeldt A, Bannenberg G, Moldeus P. Free radicals and lung disease. 1993 Br Med Bull 49:588.

198. Sandstrom J, Nilsson P, Karlsson K, Marklund S.L. 10-fold increase in human plasma extracellular superoxide dismutase content caused by a mutation in heparin-binding domain. 1994 J Biol Chem 269:19163-19166.

199. Saugstad O.D. Bronchopulmonary dysplasia and oxidative stress: Are we closer to an understanding of the pathogenesis of BPD? 1997 Acta Paediatr 86:12771282.

200. Saugstad O.D. Chronic lung disease: the role of oxidative stress. 1998 Biol Neonate 1A (Suppl l):21-28.

201. Saugstad O.D. Inhaled nitric oxide for preterm infants still an experimental therapy. 1999 Lancet 354:1047-1048.

202. Saugstad O.D. Does nitric oxide prevent oxidative mediated lung injury? 2000a Acta Paediatr 89:905-907.

203. Saugstad O.D. Therapy in free radical disease in the newborn. 2000b Current Obstetrics and Gynaecology 10:103-108.

204. Sayeed M.M. Neutrophil signaling alteration: an adverse inflammatory response after burn shock. 1998 Medicina (Buenos Aires) 58:386-392.

205. Sayeed M.M. Exuberant Ca signaling in neutrophils: a cause for concern. 2000 New Physiol Sci 15:130-136.

206. Schreck R., Rieber P., Baeuerle P.A. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa В transcription factor and HIV-1. 1991 EMBO J 10:2247-2258.

207. Schrod L., Neuhaus Т., Speer C.P., Girschick H. Possible role of uric acid as an antioxidant in premature infants. 1997 Biol Neonate 72:102-111.

208. Schubert J., Wilmer J. Does hydrogen peroxide exist "free" in biological systems? 1991 Free Radic Biol Med 11:545-555.

209. Schwartz M.D, Moore E.E., Moore F.A., Shenkar R., Moine P., Haenel J.B., Abraham E. Nuclear factor-kappaB is activated in alveolar macrophages from patients with acute respiratory distress syndrome. 1996 Crit Care Med 24:12851292.

210. Seekamp A., Mulligan M.S., Till G.O., Ward P.A. Requirements for neutrophil products and L-arginine in ischemia-reperfusion injury. 1993 Am J Pathol 142:1217-1226.

211. Selby C., MacNee W. Factors affecting neutrophil transit during acute pulmonary inflammation: minireview. 1993 Exp Lung Res 19:407-428.

212. Sen C.K. and Packer L. Antioxidant and redox regulation of gene transcription. 1996 FASEBJ 10:709-720.

213. Shau H., Butterfield L.H., Chiu R. and Kim A. Cloning and sequense analysis of candidate human natural killer-enhancing factor genes. 1994 Immunogenetics 40:129-134.

214. Shenai J.P. Vitamin A supplementation in very low birth weight neonates: rationale and evidence. 1999 Pediatrics 104 (6): 1369-1374.

215. Shi X., Mao Y., Daniel L.N, Saffiotti U, Dalai N.S, Vallyathan V. Silica radical-induced DNA damage and lipid peroxidation. 1994 Environ Health Perspect 102:149-154.

216. Shi X, Mao Y, Daniel L.N, Saffiotti U, Dalai N.S, Vallyathan V. Generation of reactive oxygen species by quartz particles and its implication for cellular damage. 1995 Appl Occup Environ Hyg 10:1138-1144.

217. Shichi H, Demar J.C. Non-selenium glutathione peroxidase without glutathione S-transferase activity from bovine ciliary body. 1990 Exp Eye Res 50:513-520.

218. Shull S, Heintz N.H, Periasamy M, et al. Differential regulation of antioxidant enzymes in response to oxidants. 1991 J Biol Chem 266:24389-24403.

219. Sibille Y, Reynolds H. Macrophages and polymorphonuclear neutrophils in lung defense and injury. 1990 Am Rev Respir Dis 141:471-501.

220. Sigalov A.B, Stern L.J. Enzymatic repair of oxidative damage to human apolipoprotein A-I. 1998 FEBS Lett 433:196-200.

221. Simeonova P.P., Luster M.I. Iron and reactive oxygen species in the asbestos-induced tumor necrosis factor-a response from alveolar macrophages. 1995 Am J Respir Cell Mol Biol 12:676-683.

222. Slot J.W., Geuze H.J, Freeman B.A, Crapo J.D. Intracellular localization of the copper-zinc and manganese superoxide dismutases in rat liver parenchymal cells. 1986 Lab Invest 55:363-371.

223. Smith L.J, Shamsuddin M, Sporn P.H, et al. Reduced superoxide dismutase in lung cells of patients with asthma. 1997 Free Radical Biol Med 22:1301.

224. Speranza M.J, Bagley A.C, Lynch R.E. Cells enriched for catalase are sensitized to the toxicities of bleomycin, adriamycin, and paraquat. 1993 J Biol Chem 268:19039-19043.

225. Spicer S.S, Schulte B.A, Chakrin L.W. Ultrastructural and histochemical observations of respiratory epithelium and gland. 1983 Lung Res 4:137-156.

226. Stancovski I. and Baltimore D. NF-кВ activation: the IkB kinase revealed? 1997 Cell 91:299-302

227. Stocker R, Yamamoto Y, McDonagh A, Glazer A, Ames B. Bilirubin is an antioxidant of possible physiological importance. 1987 Science 235:1043-1046.

228. Stralin P, Marklund S.L. Effects of oxidative stress on expression of extracellular superoxide dismutase, CuZn-superoxide dismutase and Mn-superoxide dismutase in human dermal fibroblasts. 1994 Biochem J 298:347352.

229. Strausz J., Mueller-Quernheim J., Steppling H., Ferlinz R. Oxygen radical production by alveolar inflammatory cells in idiopathic pulmonary fibrosis. 1990 Am RevRespirDis 141:124-128.

230. Streicher S.L. and Tyler B. Purification of glutamine synthetase from a variety of bacteria. mOJBacteriol 142:69-78.

231. Stroppolo M.E., Sette M., O'Neill P., Polizio F., Cambria M.T. Cu,Zn superoxide dismutase from Photobacterium leignathi is an hyperefficient enzyme. 1998 Biochemistry 37:12287-12292.

232. Sullivan S.G., Chiu D.T., Errasfa M., Wang J.M., Qi J.S., Stern A. Effects of H202 on protein tyrosine phosphatase activity in HER14 cells. 1994 Free Radic Biol Med 16:399-403.

233. Sundaresan M., Yu Z.-X., Ferrans V.J., Irani K. and Finkel T. Requirement for generation of H202 for platelet-derived growth factor signal transduction. 1995 Science 270:296-299.

234. Tekin D., Sin B.A., Mungan D., Misirligil Z., Yavuzer S. The antioxidative defense in asthma. 2000 Journal of Asthma 37(l):59-63.

235. Thannickal V.J., Fanburg B.L. Activation of an H202-generating NADH oxidase in human lung fibroblasts by transforming growth factor beta 1. 1995 J Biol Chem 270:30334-30338.

236. The Franco-Belgium Collaborative NO trial group. Early compared with delayed inhaled nitric oxide in moderately hypoxaemic neonates with respiratory failure: a randomized controlled trial. 1999 Lancet 353:1066-1071.

237. Thibeault D.W., Rezaiekhaligh M., Mabry S., Beringer T. Prevention of chronic pulmonary oxygen toxicity in young rats with liposome encapsulated catalase administered intratracheally. 1991 Pediatr Pulmonol 11:318-327.

238. Tsan M.F., White J.E., Del Vecchio P.J., Shaffer J.B. 11-6 enhances TNF-a- and II-1-induced increase of Mn superoxide dismutase mRNA and 02 tolerance. 1992 Am J Physiol 263:L22-26.

239. Vallyathan V. and Shi X. The role of oxygen free radicals in occupational and environmental lung diseases. 1997 Environ Health Perspect Suppl 105 (1) : 165177.

240. Vance С.К, Miller A.F. Spectroscopic comparisons of the pH dependence of Fe-substituted (Mn)superoxide dismutase and Fe-superoxide dismutase. 1998 Biochemistry 37:5518-5527.

241. Van der Vliet A, O'Neill C.A, Cross C.E, Koostra J.M, Volz W.G, Halliwell B, Louie S. Determination of low-molecular-mass antioxidant concentrations in human respiratory tract lining fluids. 1999 Am J Physiol 276 (Lung Cell Mol Physiol 20):L289-L296.

242. Varsila E, Pitkanen O, Hallman M, Andersson S. Immaturity-dependent free radical activity in premature infants. 1994a Pediatr Res 36:55-59.

243. Varsila E, Hallman M, Andersson S. Free-radical-induced lipid peroxidation during the early neonatal period. 1994b Acta Paediatr 83:692-695.

244. Varsila E, Pesonen E, Andersson S. Early protein oxidation in the neonatal lung is related to development of chronic lung disease. 1995 Acta Paediatr 84:12961299.

245. Verma I.M. and Stevenson J. IkB kinase: beginning, not the end. 1997 Proc Natl AcadSci USA 94:11758-11760.

246. Vile G.F, Basu-Modak S, Waltner K.C, et al. Heme oxygenase 1 mediates an adaptive response to oxidative stress in human skin fibroblasts. 1994 Proc Natl Acad Sci USA 91:2607-2610.

247. Visner G.A, Dougall W.C, Wilson J.M, Burr I.A, Nick H.S. Regulation of manganese superoxide dismutase by lipopolysaccharide, interleukin-1, and tumor necrosis factor. Role in the acute inflammatory response. 1990 J Biol Chem 265:2856-2864.

248. Ward P.A, Duque R.E, Sulavik M.C, Johnson K.J. In vitro and in vivo stimulation of rat neutrophils and alveolar macrophages by immune complexes.

249. Production of 02'~ and H202. 1983 Am J Pathol 110:297-309.

250. Warner B.B, Burhans M.S., Clark J.C, Wispe J.R. Tumor necrosis factor-alpha increases Mn-SOD expression: protection against oxidant injury. 1991 Am J Physiol 260:L296-301.

251. Watabe S, Kohno H, Kouyama H, Hiroi T, Yago N. and Nakazawa T. Purification and characterization of a substrate protein for mitochondrial ATP-dependent protease in bovine adrenal cortex. 1994 J Biochem (Tokyo) 115:648654.

252. Wen S.T., Van Etten R.A. The PAG gene product, a stress-induced protein with antioxidant properties, is an Abl SH3-binding protein and a physiological inhibitor of c-Abl tyrosine kinase activity. 1997 Genes Dev 11:2456-2467.

253. White C.W., Avraham K.B., Shanley P.F., et al. Transgenic mice with expression of elevated levels of copper-zinc superoxide dismutase in the lungs are resistant to pulmonary oxygen toxicity. 1991 J Clin Invest 87: 2162-2168.

254. Wispe J.R., Warner B.B., Clark J.C., et al. Human Mn-superoxide dismutase in pulmonary epithelial cells of transgenic mice confers protection from oxygen injury. 1992 J Biol Chem 267:23937-23941.

255. Wojtaszek P. Oxidative burst: an early plant response to pathogen infection. 1997 Biochem /322:681-692.

256. Wright D.T., Cohn L.A., Li H., Fischer В., Li C.M. and Adler K.B. Interactions of oxygen radicals with airway epithelium. 1994 Environ Health Perspect 102 (Suppl 10):85-90.

257. Yin G.Y., Yin V.F., He X.F. Effect of zhuchun pill on immunity and endocrine function of elderly with kidney-yang deficiency. 1995 Chung Kuo Chung Hsi I ChiehHo Tsa Chih 15:601-603.

258. Yu B.P. Cellular defenses against damage from reactive oxygen species. 1994 Physiol Rev 74:139-162.

259. Zhang P., Liu В., Kang S.W., Seo M.S., Rhee S.G. and Obeid L.M. Thioredoxin peroxidase is a novel inhibitor of apoptosis with a mechanism distinct from that of Bcl-2. 1997 J Biol Chem 272:30615-30618.

260. Zhao Y., Gilmore B.J., Young S.L. Expression of transforming growth factor-(3 receptors during hyperoxia-induced lung injury and repair. 1997 Am J Physiol 273 (Lung CellMol Physiol 17):L355-L362.

261. Zor U., Ferber E., Gergely P., Szucs K., Dombradi V., Goldman R. Reactive oxygen species mediate phorbol ester-regulated tyrosine phosphorylation and phospholipase A2 activation: potentiation by vanadate. 1993 Biochem J 295:879-888.

262. Выражаю глубокую благодарность моему научному руководителю д.б.н., профессору Владимиру Ивановичу Новосёлову за предоставленную интересную тему диссертации, внимательное руководство и непосредственное участие в экспериментальной работе.

263. Особую благодарность хочу выразить моему руководителю к.б.н. Владимиру Борисовичу Садовникову за проявленное внимание и практическую помощь в работе с животными.

264. Хочу поблагодарить к.б.н. Сафронову Валентину Григорьевну, с.н.с. лаборатории биофизики нервной клетки ИБК РАН, за любезно предоставленные реактивы и оборудование и помощь в проведении экспериментов по исследованию функциональной активности нейтрофилов.

265. Искреннюю признательность выражаю моей сестре Наталье Николаевне Кравченко и её супругу Александру Сергеевичу Кутузову за теплую поддержку и помощь, оказанную в оформлении работы.

266. Также хочу выразить благодарность всем сотрудникам лаборатории биофизики рецепции ИБК РАН и коллегам лаборатории биологических испытаний ФИБХ РАН за помощь и моральную поддержку, которые помогли выполнить эту работу.