DOI QR코드

DOI QR Code

Exercise and Reactive Oxygen Species

운동과 활성산소

  • Kim, Hye Jin (Department of Kinesiology and Sports Studies, College of Science and Industry Convergence, Ewha Womans University) ;
  • Lee, Won Jun (Department of Kinesiology and Sports Studies, College of Science and Industry Convergence, Ewha Womans University)
  • 김혜진 (이화여자대학교 신산업융합대학 체육과학과) ;
  • 이원준 (이화여자대학교 신산업융합대학 체육과학과)
  • Received : 2017.07.03
  • Accepted : 2017.09.25
  • Published : 2017.09.30

Abstract

Free radicals have long been considered damaging to various tissues. An excessive amount of reactive oxygen species (ROS) is known to have detrimental effects on the body and to be linked to numerous pathological conditions, such as cardiovascular disease, cancer, diabetes, and skeletal muscle atrophy. On the other hand, recent findings suggest that ROS is important for maintenance and development of cellular activity. Cells respond to increased oxidative stress by adaptive changes in the expression of a variety of proteins involved in the maintenance of cellular integrity. ROS is also essential for skeletal muscle function and metabolism. It is well known that physical exercise has many health benefits. Paradoxically, physical exercise also stimulates the production of ROS, which result in oxidative stress. Based on evidence amassed in the past decade, exercise itself may be considered an antioxidant because training increases the expression of antioxidant enzymes. In this review, we discuss the processes underlying the generation of ROS and its role in exercise-induced adaptation based on recent evidence. Furthermore, we discuss the possible role of NADPH oxidase in exercise-induced activation of insulin signaling and its effect on longevity.

활성산소란 세포에 손상을 가하는 모든 종류의 변형된 산소를 의미하며, 활성산소 생성의 증가는 세포 내의 산화적 스트레스를 유발하여 심혈관 질환, 암, 당뇨, 근위축 등 각종 질병의 원인이 된다. 그러나 적정 수준의 활성산소는 세포의 성장 및 발달에 중요한 역할을 담당하는 것으로 보고되어 있으며, 골격근에서의 활성산소는 근기능과 대사에 필수적인 역할을 담당한다. 규칙적인 운동은 건강상 다양한 이점을 가져다주지만, 과도한 운동은 골격근을 비롯한 다양한 체내 조직에서 활성산소의 생성을 증가시키며, 고농도의 활성산소 생성은 세포 손상을 일으키는 것으로 보고되고 있다. 따라서 운동에 의한 활성산소의 생성 증가와 그에 따른 분자적 기전은 운동이 주는 건강상의 많은 이점들을 이해하는데 있어 중요한 기전으로 받아들여지고 있다. 최근 운동 강도나 형태에 따른 활성산소의 생성 수준과 근육 관련 유전자 발현 및 대사 관련 연구에 있어 활성산소의 역할에 관한 연구들이 활발히 이루어지고 있지만 심도 있는 기전적 연구와 이해는 부족한 실정이다. 따라서 본 총설에서는 운동에 의한 활성산소 생성 기전과 그에 따른 역할에 대한 선행 연구들을 살펴보고, 운동에 의한 인슐린 신호체계의 활성 및 그에 따른 수명 조절에 있어 NADPH 산화효소의 역할에 대해서도 살펴보았다.

Keywords

References

  1. Adams, V., Linke, A., Krankel, N., Erbs, S., Gielen, S., Mobius-Winkler, S., Gummert, J. F., Mohr, F. W., Schuler, G. and Hambrecht, R. 2005. Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease. Circulation 111, 555-562. https://doi.org/10.1161/01.CIR.0000154560.88933.7E
  2. Adhihetty, P. J., Irrcher, I., Joseph, A. M., Ljubicic, V. and Hood, D. A. 2003. Plasticity of skeletal muscle mitochondria in response to contractile activity. Exp. Physiol. 88, 99-107. https://doi.org/10.1113/eph8802505
  3. Albanes, D., Heinonen, O. P., Taylor, P. R., Virtamo, J., Edwards, B. K., Rautalahti, M., Hartman, A. M., Palmgren, J., Freedman, L. S., Haapakoski, J., Barrett, M. J., Pietinen, P., Malila, N., Tala, E., Liippo, K., Salomaa, E. R., Tangrea, J. A., Teppo, L., Askin, F. B., Taskinen, E., Erozan, Y., Greenwald, P. and Huttunen, J. K. 1996. Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J. Natl. Cancer Inst. 88, 1560-1570. https://doi.org/10.1093/jnci/88.21.1560
  4. Amezian-El Hassani, R. A., Benfares, N., Caillou, B., Talbot, M., Sabourin, J. C., Belotte, V., Morand, S., Gnidehou, S., Agnandji, D., Ohayon, R., Kaniewski, J., Noel-Hudson, M. S., Bidart, J. M., Schlumberger, M., Virion, A. and Dupuy, C. 2005. Dual oxidase2 is expressed all along the digestive tract. Am. J. Physiol. 288, G933-942.
  5. Avery, N. G., Kaiser, J. L., Sharman, M. J., Scheett, T. P., Barnes, D. M., Gomez, A. L., Kraemer, W. J. and Volek, J. S. 2003. Effects of vitamin E supplementation on recovery from repeated bouts of resistance exercise. J. Strength. Cond. Res. 17, 801-809.
  6. Bae, Y. S., Choi, M. K. and Lee, W. J. 2010. Dual oxidase in mucosal immunity and host-microbe homeostasis. Trends. Immunol. 7, 278-287.
  7. Banfi, B., Maturana, A., Jaconi, S., Arnaudeau, S., Laforge, T., Sinha, B., Ligeti, E., Demaurex, N. and Krause, K. H. 2000. A mammalian H+ channel generated through alternative splicing of the NADPH oxidase homolog NOH-1. Science 287, 138-142. https://doi.org/10.1126/science.287.5450.138
  8. Barbieri, E. and Sestili, P. 2012. Reactive oxygen species in skeletal muscle signaling. J. Signal Transduct. 2012, 982794.
  9. Bashan, N., Kovsan, J., Kachko, I., Ovadia, H. and Rudich, A. 2009. Positive regulation of insulin signaling by reactive oxygen species. Physiol. Rev. 89, 27-71. https://doi.org/10.1152/physrev.00014.2008
  10. Bjelakovic, G., Nikolova, D., Simonetti, R. G. and Gluud, C. 2004. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 364, 1219-1228. https://doi.org/10.1016/S0140-6736(04)17138-9
  11. Cherednichenko, G., Zima, A. V., Feng, W., Schaefer, S., Blatter, L. A. and Pessah, I. N. 2004. NADH oxidase activity of rat cardiac sarcoplasmic reticulum regulates calcium-induced calcium release. Circ. Res. 94, 478-486. https://doi.org/10.1161/01.RES.0000115554.65513.7C
  12. Childs, A., Jacobs, C., Kaminski, T., Halliwell, B. and Leeuwenburgh, C. 2001. Supplementation with vitamin C and N-acetyl-cysteine increases oxidative stress in humans after an acute muscle injury induced by eccentric exercise. Free. Radic. Biol. Med. 31, 745-753. https://doi.org/10.1016/S0891-5849(01)00640-2
  13. Close, G. L., Ashton, T., Cable, T., Doran, D., Holloway, C., McArdle, F. and MacLaren, D. P. 2006. Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process. Br. J. Nutr. 95, 976-981. https://doi.org/10.1079/BJN20061732
  14. Davies, K. J., Quintanilha, A. T., Brooks, G. A. and Packer, L. 1982. Free radicals and tissue damage produced by exercise. Biophys. Res. Commun. 107, 1198-1205. https://doi.org/10.1016/S0006-291X(82)80124-1
  15. De Deken, X., Wang, D., Many, M. C., Costagliola, S., Libert, F., Vassart, G., Dumont, J. E. and Miot, F. 2000. Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family. J. Biol. Chem. 275, 23227-23233. https://doi.org/10.1074/jbc.M000916200
  16. Dillard, C. J., Litov, R. E., Savin, W. M., Dumelin, E. E. and Tappel, A. L. 1978. Effects of exercise, vitamin E, ozone on pulmonary function and lipid peroxidation. J. Appl. Physiol. 45, 927-932. https://doi.org/10.1152/jappl.1978.45.6.927
  17. Dupuy, C., Ohayon, R., Valent, A., Noel-Hudson, M. S., Dème, D. and Virion, A. 1999. Purification of a novel flavo protein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cDNAs. J. Biol. Chem. 274, 37265-37269. https://doi.org/10.1074/jbc.274.52.37265
  18. Durrant, J. R., Seals, D. R., Connell, M. L., Russell, M. J., Lawson, B. R., Folian, B. J., Donato, A. J. and Lesniewski, L. A. 2009. Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase. J. Physiol. 587, 3271-3285. https://doi.org/10.1113/jphysiol.2009.169771
  19. Duthie, G. G., Robertson, J. D., Maughan, R. J. and Morrice, P. C. 1990. Blood antioxidant status and erythrocyte lipid peroxidation following distance running. Arch. Biochem. Biophys. 282, 78-83. https://doi.org/10.1016/0003-9861(90)90089-H
  20. Eckel, R. H., Grundy, S. M. and Zimmet, P. Z. 2005. The metabolic syndrome. Lancet 365, 1415-1428. https://doi.org/10.1016/S0140-6736(05)66378-7
  21. Fischer, H. 2009. Mechanisms and function of DUOX in epithelia of the lung. Antioxid. Redox. Signal. 11, 2453-2465. https://doi.org/10.1089/ars.2009.2558
  22. Gomes, E. C., Silva, A. N. and de Oliveira, M. R. 2012. Oxidants, antioxidants, and the beneficial roles of exerciseinduced production of reactive species. Oxid. Med. Cell. Longev. 756132, 1-12.
  23. Ha, E. M., Oh, C. T., Bae, Y. S. and Lee, W. J. 2005. A direct role for dual oxidase in Drosophila gut immunity. Science 4, 847-850.
  24. Ha, E. M., Lee, K. A., Park, S. H., Kim, S. H., Nam, H. J., Lee, H. Y., Kang, D. and Lee, W. J. 2009. Regulation of DUOX by the Galphaq phospholipase C beta-Ca2+ pathway in Drosophila gut immunity. Dev. Cell. 16, 386-397. https://doi.org/10.1016/j.devcel.2008.12.015
  25. Handayaningsih, A. E., Iguchi, G., Fukuoka, H., Nishizawa, H., Takahashi, M., Yamamoto, M., Herningtyas, E. H., Okimura, Y., Kaji, H., Chihara, K., Seino, S. and Takahashi, Y. 2011. Reactive oxygen species play an essential role in IGF-I signaling and IGF-I-induced myocyte hypertrophy in C2C12 myocytes. Endocrinology 152, 912-921. https://doi.org/10.1210/en.2010-0981
  26. Jackson, M. J., Pye, D. and Palomero, J. 2007. The production of reactive oxygen and nitrogen species by skeletal muscle. J. Appl. Physiol. 102, 1664-1670. https://doi.org/10.1152/japplphysiol.01102.2006
  27. Kanter, M. 1995. Free radicals and exercise: effects of nutritional antioxidant supplementation. Exerc. Sport. Sci. Rev. 23, 375-397.
  28. Kasapis, C. and Thompson, P. D. 2005. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J. Am. Coll. Cardiol. 45, 1563-1569. https://doi.org/10.1016/j.jacc.2004.12.077
  29. Katsuyama, M., Matsuno, K. and Yabe-Nishimura, C. 2012. Physiological roles of NOX/NADPH oxidase, the superoxide-generating enzyme. J. Clin. Biochem. Nutr. 50, 9-22.
  30. Lambeth, J. D. 2004. NOX enzymes and the biology of reactive oxygen. Nat. Rev. Immunol. 4, 181-189. https://doi.org/10.1038/nri1312
  31. Lawler, J. M., Powers, S. K., Van Dijk, H., Visser, T., Kordus, M. J. and Ji, L. L. 1994. Metabolic and antioxidant enzyme activities in the diaphragm: effects of acute exercise. Respir. Physiol. 96, 139-149. https://doi.org/10.1016/0034-5687(94)90122-8
  32. Leto, T. L. and Geiszt, M. 2006. Role of Nox family NADPH oxidases in host defense. Antioxid. Redox. Signal. 8, 1549-1561. https://doi.org/10.1089/ars.2006.8.1549
  33. Matsumoto, H., Takenami, E., Iwasaki-Kurashige, K., Osada, T., Katsumura, T. and Hamaoka, T. 2005. Effects of blackcurrant anthocyanin intake on peripheral muscle circulation during typing work in humans. Eur. J. Appl. Physiol. 94, 36-45. https://doi.org/10.1007/s00421-004-1279-y
  34. Moreno, J. C., Bikker, H., Kempers, M. J., van Trotsenburg, A. S., Baas, F., de Vijlder, J. J., Vulsma, T. and Ris-Stalpers, C. 2002. Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. N. Engl. J. Med. 347, 95-102. https://doi.org/10.1056/NEJMoa012752
  35. Nikolaidis, M. G. and Jamurtas, A. Z. 2009. Blood as a reactive species generator and redox status regulator during exercise. Arch. Biochem. Biophys. 490, 77-84. https://doi.org/10.1016/j.abb.2009.08.015
  36. Olefsky, J. M. 2008. Fat talks, liver and muscle listen. Cell 134, 914-916. https://doi.org/10.1016/j.cell.2008.09.001
  37. Peternelj, T. T. and Coombes, J. S. 2011. Antioxidant supplementation during exercise training: beneficial or detrimental? Sports Med. 41, 1043-1069. https://doi.org/10.2165/11594400-000000000-00000
  38. Phillips, J. P., Campbell, S. D., Michaud, D., Charbonneau, M. and Hilliker, A. J. 1989. Null mutation of copper/zinc superoxide dismutase in Drosophila confers hypersensitivity to paraquat and reduced longevity. Proc. Natl. Acad. Sci. USA 86, 2761-2765. https://doi.org/10.1073/pnas.86.8.2761
  39. Pillon, N. J., Bilan, P. J., Fink, L. N. and Klip, A. 2013. Cross-talk between skeletal muscle and immune cells: muscle-derived mediators and metabolic implications. Am. J. Physiol. 304, E453-465.
  40. Powers, S. K. and Jackson, M. J. 2008. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol. Rev. 88, 1243-1276. https://doi.org/10.1152/physrev.00031.2007
  41. Powers, S. K., Nelson, W. B. and Hudson, M. B. 2011. Exercise-induced oxidative stress: Cause and consequences. Free. Radic. Biol. Med. 51, 942-950. https://doi.org/10.1016/j.freeradbiomed.2010.12.009
  42. Reddy, V. P., Zhu, X., Perry, G. and Smith, M. A. 2009. Oxidative stress in diabetes and Alzheimer's disease. J. Alzheimers. Dis. 16, 763-774. https://doi.org/10.3233/JAD-2009-1013
  43. Reid, M. B., Khawli, F. A. and Moody, M. R. 1993. Reactive oxygen in skeletal muscle. III. Contractility of unfatigued muscle. J. Appl. Physiol. 75, 1081-1087. https://doi.org/10.1152/jappl.1993.75.3.1081
  44. Reid, M. B. and Moody, M. R. 1994. Dimethyl sulfoxide depresses skeletal muscle contractility. J. Appl. Physiol. 76, 2186-2190. https://doi.org/10.1152/jappl.1994.76.5.2186
  45. Reid, M. B., Stokic, D. S., Koch, S. M., Khawli, F. A. and Leis, A. A. 1994. N-acetylcysteine inhibits muscle fatigue in humans. J. Clin. Invest. 94, 2468-2474. https://doi.org/10.1172/JCI117615
  46. Reid, M. B., Kobzik, L., Bredt, D. S. and Stamler, J. S. 1998. Nitric oxide modulates excitation-contraction coupling in the diaphragm. Comp. Biochem. Physiol. A. Mol. Intergr. Physiol. 119, 211-218. https://doi.org/10.1016/S1095-6433(97)00417-0
  47. Rhee, S. G., Bae, Y. S., Lee, S. R. and Kwon, J. 2000. Hydrogen peroxide: a key messenger that modulates protein phosphorylation through cysteine oxidation. Sci. STKE. 2000, pe1.
  48. Ristow, M. and Schmeisser, S. 2011. Extending lifespan by increasing oxidative stress. Free. Radic. Biol. Med. 51, 327-336. https://doi.org/10.1016/j.freeradbiomed.2011.05.010
  49. Sandstrom, M. E., Zhang, S. J. and Bruton, J. 2006. Role of reactive oxygen species in contraction-dedicated glucose transport in mouse skeletal muscle. J. Physiol. 575, 251-262. https://doi.org/10.1113/jphysiol.2006.110601
  50. Schulz, T. J., Zarse, K., Voigt, A., Urban, N., Birringer, M. and Ristow, M. 2007. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell. Metab. 6, 280-293. https://doi.org/10.1016/j.cmet.2007.08.011
  51. Seals, D. R., Walker, A. E., Pierce, G. L. and Lesniewski, L. A. 2009. Habitual exercise and vascular ageing. J. Physiol. 587, 5541-5549. https://doi.org/10.1113/jphysiol.2009.178822
  52. Sestili, P., Barbieri, E., Martinelli, C., Battistelli, M., Guescini, M., Vallorani, L., Casadei, L., D'Emilio, A., Falcieri, E., Piccoli, G., Agostini, D., Annibalini, G., Paolillo, M., Gioacchini, A. M. and Stocchi, V. 2009. Creatine supplementation prevents the inhibition of myogenic differentiation in oxidatively injured C2C12 murine myoblasts. Mol. Nutr. Food. Res. 53, 1187-1204. https://doi.org/10.1002/mnfr.200800504
  53. Shao, M. X. and Nadel, J. A. 2005. Dual oxidase 1-dependent MUC5AC mucin expression in cultured human airway epithelial cells. Proc. Natl. Acad. Sci. USA 102, 767-772. https://doi.org/10.1073/pnas.0408932102
  54. Suh, Y. A., Arnold, R. S., Lassegue, B., Shi, J., Xu, X., Sorescu, D., Chung, A. B., Griendling, K. K. and Lambeth, J. D. 1999. Cell transformation by the superoxide-generating oxidase Mox1. Nature 401, 79-82. https://doi.org/10.1038/43459
  55. Tidball, J. G. 2005. Inflammatory processes in muscle injury and repair. Am. J. Physiol. 288, R345-353.
  56. Trott, D. W., Gunduz, F., Laughlin, M. H. and Woodman, C. R. 2009. Exercise training reverses age-related decrements in endothelium-dependent dilation in skeletal muscle feed arteries. J. Appl. Physiol. 106, 1925-1934. https://doi.org/10.1152/japplphysiol.91232.2008
  57. Urso, M. L. and Clarkson, P. M. 2003. Oxidative stress, exercise, and antioxidant supplementation. Toxicology 189, 41-54. https://doi.org/10.1016/S0300-483X(03)00151-3
  58. Van der Vliet, A. 2008. NADPH oxidases in lung biology and pathology: host defense enzymes, and more. Free. Radic. Biol. Med. 44, 938-955. https://doi.org/10.1016/j.freeradbiomed.2007.11.016