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Analysis of cellular responses to free radicals: focus on exercise and skeletal muscle

Published online by Cambridge University Press:  12 June 2007

Scott K. Powers  and
Shannon L. Lennon
Scott K. Powers*
Affiliation:
Departments of Exercise and Sport Sciences and Physiology, Center for Exercise Science, University of Florida, Gainesville, Florida 32611, USA
Shannon L. Lennon
Affiliation:
Departments of Exercise and Sport Sciences and Physiology, Center for Exercise Science, University of Florida, Gainesville, Florida 32611, USA
*
*Corresponding Author: Professor Scott K. Powers, fax +1 352 392 0316, email spowers@hhp.ufl.edu
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Abstract

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Muscular exercise results in an increased production of radicals and other forms of reactive oxygen species (ROS). Recent evidence suggests that radicals and other ROS are an underlying aetiology in exercise-induced disturbances in muscle redox status. These exercise-induced redox disturbances in skeletal muscle are postulated to contribute to both muscle fatigue and/or exercise-induced muscle injury. To defend against ROS, muscle cells contain complex cellular defence mechanisms to reduce the risk of oxidative injury. Two major classes (enzymic and non-enzymic) of endogenous protective mechanisms work together to reduce the harmful effects of oxidants in the cell. Primary antioxidant enzymes include superoxide dismutase (EC 1.15.1.1; SOD), GSH peroxidase (EC 1.11.1.9; GPX), and catalase (EC 1.11.1.6); these enzymes are responsible for removing superoxide radicals, H2O2 and organic hydroperoxides, and H2O2 respectively. Important non-enzymic antioxidants include vitamins E and C, β-carotene, GSH and ubiquinones. Vitamin E, β-carotene and ubiquinone are located in lipid regions of the cell, whereas GSH and vitamin C are in aqueous compartments of the cell. Regular endurance training promotes an increase in both total SOD and GPX activity in actively-recruited skeletal muscles. High-intensity exercise training has been shown to be generally superior to low-intensity exercise in the upregulation of muscle SOD and GPX activities. Also, training-induced upregulation of antioxidant enzymes is limited to highly-oxidative skeletal muscles. The effects of endurance training on non-enzymic antioxidants remain a relatively uninvestigated area.

Keywords

Oxidative stressExerciseSkeletal muscleFree radicalsReactive oxygen species

Information

Type
Meeting Report
Information
Proceedings of the Nutrition Society , Volume 58 , Issue 4 , November 1999 , pp. 1025 - 1033
Copyright
The Nutrition Society

References

Aberg, F, Appelkvist, EL, Dallner, G & Ernster, L (1992) Distribution and redox state of ubiquinones in rat and human tissues. Archives of Biochemistry and Biophysics 295, 230–234.CrossRefGoogle ScholarPubMed
Alessio, H & Goldfarb, A (1988) Lipid peroxidation and scavenger enzymes during exercise: adaptive response to training. Journal of Applied Physiology 64, 1333–1336.CrossRefGoogle ScholarPubMed
Armstrong, R & Phelps, R (1984) Muscle fiber type composition of the rat hindlimb. American Journal of Anatomy 171, 259–272.CrossRefGoogle ScholarPubMed
Barclay, JK & Hansel, M (1991) Free radicals may contribute to oxidative skeletal muscle fatigue. Canadian Journal of Physiology and Pharmacology 69, 279–284.CrossRefGoogle ScholarPubMed
Beyer, RE, Morales-Corral, P, Ramp, B, Kreitman, KR, Falzon, MJ, Rhee, SY, Kuhn, TW, Stein, M, Rosenwasser, MJ & Cartwright, KJ (1984) Elevation of tissue coenzyme Q (ubiquinone) and cytochrome C concentrations by endurance exercise in the rat. Archives of Biochemistry and Biophysics 234, 323–329.CrossRefGoogle ScholarPubMed
Borzone, G, Zhao, B, Merola, AJ, Berliner, L & Clanton, TL (1994) Detection of free radicals by electron spin resonance in rat diaphragm after resistive loading. Journal of Applied Physiology 77, 812–818.CrossRefGoogle ScholarPubMed
Bowles, DK, Torgan, CE, Ebner, S, Kehrer, JP, Ivy, JL & Staines, JW (1991) Effects of acute, submaximal exercise on skeletal muscle vitamin E. Free Radical Research Communications 14, 139–143.CrossRefGoogle ScholarPubMed
Burton, GW & Ingold, KU (1989) Vitamin E as an in vitro and in vivo antioxidant. Annals of the New York Academy of Sciences 570, 7–22.CrossRefGoogle ScholarPubMed
Burton, GW & Traber, MG (1990) Vitamin E: antioxidant activity, biokinetics, and bioavailability. Annual Review of Nutrition 10, 357–382.CrossRefGoogle ScholarPubMed
Criswell, D, Powers, S, Dodd, S, Lawler, J, Edwards, W, Renshler, K & Grinton, S (1993) High intensity training-induced changes in skeletal muscle antioxidant activity. Medicine and Science in Sports and Exercise 25, 1135–1140.CrossRefGoogle Scholar
Davies, KJ, Quintanilha, AT, Brooks, GA & Packer, L (1982) Free radicals and tissue damage produced by exercise. Biochemical and Biophysical Research Communications 107, 1198–1205.CrossRefGoogle ScholarPubMed
Gohil, K, Packer, L, deLumen, B, Brooks, GA & Terblanche, SE (1986) Vitamin E deficiency and vitamin C supplements: exercise and mitochondrial oxidation. Journal of Applied Physiology 60, 1986–1991.CrossRefGoogle ScholarPubMed
Gohil, K, Rothfuss, L, Lang, J & Packer, L (1987) Effect of exercise training on tissue vitamin E and ubiquinone content. Journal of Applied Physiology 63, 1638–1641.CrossRefGoogle ScholarPubMed
Grisham, M & McCord, J (1986) Physiology of Oxygen Radicals.Baltimore, MD: Williams and Wilkins.Google Scholar
Halliwell, B & Gutteridge, JM (editors) (1989) Iron toxicity and oxygen radicals. In Free Radicals in Biology and Medicine, 2nd ed., pp. 86–123.Oxford: Clarendon Press.Google Scholar
Hammeren, J, Powers, S, Lawler, J, Criswell, D, Martin, D, Lowenthal, D & Pollock, M (1992) Exercise training-induced alterations in skeletal muscle oxidative and antioxidant enzyme activity in senescent rats. International Journal of Sports Medicine 13, 412–416.CrossRefGoogle ScholarPubMed
Hellsten, Y, Apple, F & Sjodin, B (1996) Effect of sprint cycle training on activities of antioxidant enzymes in human skeletal muscle. Journal of Applied Physiology 81, 1484–1487.CrossRefGoogle ScholarPubMed
Higuchi, M, Cartier, LJ, Chen, M & Holloszy, JO (1985) Superoxide dismutase and catalase in skeletal muscle: adaptive response to exercise. Journal of Gerontology 40, 281–286.CrossRefGoogle ScholarPubMed
Jackson, M (1998) Free radical mechanisms in exercise-related muscle damage. In Oxidative Stress in Skeletal Muscle, pp. 75–86 [Reznick, AZ, Packer, L, Sen, CK, Holloszy, JO and Jackson, MJ, editors]. Basel: Birkhauser Verlag.CrossRefGoogle Scholar
Jackson, MJ, Edwards, RH & Symons, MC (1985) Electron spin resonance studies of intact mammalian skeletal muscle. Biochimica et Biophysica Acta 847, 185–190.CrossRefGoogle ScholarPubMed
Janero, DR (1991) Therapeutic potential of vitamin E against myocardial ischemic-reperfusion injury. Free Radical Biology and Medicine 10, 315–324.CrossRefGoogle ScholarPubMed
Jenkins, R (1983) The role of superoxide dismutase and catalase in muscle fatigue. In Biochemistry of Exercise, Vol.13, pp. 467–471 [Knuttgen, H, editor]. Champaign, IL: Human Kinetics Publishers.Google Scholar
Ji, LL (1995a) Exercise and oxidative stress: role of the cellular antioxidant systems. Exercise and Sport Science Reviews 23, 135–166.CrossRefGoogle ScholarPubMed
Ji, LL (1995b) Oxidative stress during exercise: implication of antioxidant nutrients. Free Radical Biology and Medicine 18, 1079–1086.CrossRefGoogle ScholarPubMed
Ji, LL, Fu, R & Mitchell, E (1992) Glutathione and antioxidant enzymes in skeletal muscle: effects of fiber type and exercise intensity. Journal of Applied Physiology 73, 1854–1859.CrossRefGoogle ScholarPubMed
Ji, LL, Stratman, F & Lardy, H (1988) Antioxidant enzyme systems in rat liver and skeletal muscle. Archives of Biochemistry and Biophysics 263, 150–160.CrossRefGoogle ScholarPubMed
Kagan, VE, Bakalova, RA, Serbinova, EE & Stoytchev, TS (1990) Fluorescence measurements of incorporation and hydrolysis of tocopherol and tocopheryl esters in biomembranes. Methods in Enzymology 186, 355–367.CrossRefGoogle ScholarPubMed
Kagan, VE, Shvedova, A, Serbinova, E, Khan, S, Swanson, C, Powell, R & Packer, L (1992) Dihydrolipoic acid-a universal antioxidant both in the membrane and in the aqueous phase. Reduction of peroxyl, ascorbyl and chromanoxyl radicals. Biochemistry and Pharmacology 44, 1637–1649.CrossRefGoogle ScholarPubMed
Karlsson, J, Lin, L & Sylven, C (1996) Muscle ubiquinone in healthy physically active males. Molecular and Cellular Biochemistry 156, 169–172.CrossRefGoogle ScholarPubMed
Krinsky, NI & Deneke, SM (1982) Interaction of oxygen and oxy-radicals with carotenoids. Journal of the National Cancer Institute 69, 205–210.Google ScholarPubMed
Laughlin, MH, Simpson, T, Sexton, WL, Brown, OR, Smith, JK & Korthuis, KJ (1990) Skeletal muscle oxidative capacity, antioxidant enzymes, and exercise training. Journal of Applied Physiology 68, 337–343.CrossRefGoogle ScholarPubMed
Lawler, J, Powers, S & Criswell, D (1993) Inducibility of NADP-specific isocitrate dehydrogenase with endurance training in skeletal muscle. Acta Physiologica Scandinavica 149, 177–181.CrossRefGoogle ScholarPubMed
Leeuwenburg, C, Fiebig, R, Chandwaney, R & Ji, LL (1994) Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems. American Journal of Physiology 267, R439–R445.Google Scholar
Leeuwenburgh, C, Hollander, J, Fiebig, R, Leichtweis, S, Griffith, M & Li, JJ (1997) Adaptations of glutathione antioxidant system to endurance training are tissue and muscle fiber specific. American Journal of Physiology 272, R363–R369.Google ScholarPubMed
Marin, E, Kretzschmar, M, Arokoski, J, Hanninen, O & Klinger, W (1993) Enzymes of glutathione synthesis in dog skeletal muscles and their response to training. Acta Physiologica Scandinavica 47, 369–373.CrossRefGoogle Scholar
Meister, A & Anderson, ME (1983) Glutathione. Annual Reviews of Biochemistry 52, 711–760.CrossRefGoogle ScholarPubMed
Mellors, A & Tappel, AL (1966) The inhibition of mitochondrial peroxidation by ubiquinone and ubiquinol. Journal of Biological Chemistry 241, 4353–4356.CrossRefGoogle ScholarPubMed
Meydani, M, Evans, W, Handelman, G, Biddle, L, Fielding, RA, Meydani, SN, Burrill, J, Fiatarone, MA, Blumberg, JB & Cannon, JG (1993) Protective effect of vitamin E on exercise-induced oxidative damage in young and older adults. American Journal of Physiology 264, R992–R998.Google ScholarPubMed
Nashawati, E, Dimarco, A & Supinski, G (1993) Effects produced by infusion of a free radical-generating solution into the diaphragm. American Review of Respiratory Disease 147, 60–65.CrossRefGoogle ScholarPubMed
Novelli, GP, Bracciotti, G & Falsini, S (1990) Spin-trappers and vitamin E prolong endurance to muscle fatigue in mice. Free Radical Biology and Medicine 8, 9–13.CrossRefGoogle ScholarPubMed
Oberly, L, St, Clair D, Autor, A & Oberly, T (1987) Increase in manganese superoxide dismutase activity in the mouse heart after X-irradiation. Archives of Biochemistry and Biophysics 254, 69–80.CrossRefGoogle Scholar
Oh-ishi, S, Kizaki, T, Nagasawa, J, Izawa, T, Komabayashi, T, Nagata, N, Suzuki, K, Taniguchi, N & Ohno, H (1997a) Effects of endurance training on superoxide dismutase activity, content and mRNA expression in rat muscle. Clinical and Experimental Pharmacology and Physiology 5, 326–332.CrossRefGoogle Scholar
Oh-ishi, S, Kizaki, T, Ookawara, T, Sakurai, T, Izawa, T, Nagata, N & Ohno, H (1997b) Endurance training improves the resistance of rat diaphragm to exercise-induced oxidative stress. American Journal of Respiratory and Critical Care Medicine 156, 1579–1585.CrossRefGoogle ScholarPubMed
Ohno, H, Suzuki, K, Ffujii, J, Yamashita, H, Kizaki, T, Oh-ishi, S & Taniguchi, N (1994) Exercise and Oxygen Toxicity. Amsterdam: Elsevier Publishers.Google Scholar
O'Neill, CA, Stebbins, CL, Bonigut, S, Halliwell, B & Longhurst, JC (1996) Production of hydroxyl radicals in contracting skeletal muscle of cats. Journal of Applied Physiology 81, 1197–1206.CrossRefGoogle ScholarPubMed
Oyanuagui, Y (1984) Reevaluation of assay methods and establishment of kit for superoxide dismutase activity. Analytical Biochemistry 142, 290–296.CrossRefGoogle Scholar
Packer, L (1991) Protective role of vitamin E in biological systems. American Journal of Clinical Nutrition 53, 1050S–1055S.CrossRefGoogle ScholarPubMed
Packer, L (1994) Antioxidant properties of lipoic acid and its therapeutic effects in prevention of diabetes complications and cataracts. Annals of the New York Academy of Sciences 738, 257–264.CrossRefGoogle ScholarPubMed
Packer, L, Almada, A & Rothfuss, L (1989) Modulation of tissue vitamin E levels by physical exercise. Annals of the New York Academy of Sciences 570, 311–321.CrossRefGoogle ScholarPubMed
Packer, JE, Slater, TF & Willson, RL (1979) Direct observation of a free radical interaction between vitamin E and vitamin C. Nature 278, 737–738.CrossRefGoogle ScholarPubMed
Pette, D & Dusterhoft, S (1992) Altered gene expression in fast-twitch induced by chronic low-frequency stimulation. American Journal of Physiology 262, R333–R338.Google ScholarPubMed
Powers, S, Criswell, D, Lawler, J, Ji, L, Martin, D, Herb, R & Dudley, G (1994a) Influence of exercise and fiber type on antioxidant enzyme activity in rat skeletal muscle. American Journal of Physiology 266, R375–R380.Google ScholarPubMed
Powers, S, Criswell, D, Lawler, J, Martin, D, Ji, L, Herb, R & Dudley, G (1994b) Regional training-induced alterations in diaphragmatic oxidative and antioxidant enzymes. Respiration Physiology 95, 227–237.CrossRefGoogle ScholarPubMed
Powers, S, Ji, C & Leeuwenburgh, C (1999) Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review. Medicine and Science in Sports and Exercise(In the Press).Google Scholar
Powers, S, Lawler, J, Criswell, D, Lieu, F-K & Martin, D (1992) Aging and respiratory muscle metabolic plasticity: effects of endurance training. Journal of Applied Physiology 72, 1068–1073.CrossRefGoogle ScholarPubMed
Powers, S & Sen, C (1999) Physiological antioxidants and exercise training. In Exercise and Oxygen Toxicity [Sen, C and Packer, L, editors]. Amsterdam: Elsevier (In the Press).Google Scholar
Reid, M, Haack, K, Franchek, K, Valberg, PA, Kobzik, L & West, MS (1992a) Reactive oxygen in skeletal muscle: I. Intracellular oxidant kinetics and fatigue in vitro. Journal of Applied Physiology 73, 1797–1804.CrossRefGoogle ScholarPubMed
Reid, M, Shoji, T, Moody, M & Entman, ML (1992b) Reactive oxygen in skeletal muscle. II. Extracellular release of free radicals. Journal of Applied Physiology 73, 1805–1809.CrossRefGoogle ScholarPubMed
Reid, MB, Stokic, DS, Koch, SM, Khawli, FA & Leis, AA (1994) N-acetylcysteine inhibits muscle fatigue in humans. Journal of Clinical Investigation 94, 2468–2474.CrossRefGoogle ScholarPubMed
Salminen, A & Vihko, V (1983) Endurance training reduces the susceptibility of mouse skeletal muscle to lipid peroxidation in vitro. Acta Physiologica Scandinavica 117, 109–113.CrossRefGoogle ScholarPubMed
Sen, CK, Marin, E, Kretzschmar, M & Hanninen, O (1992) Skeletal muscle and liver glutathione homeostasis in response to training, exercise, and immobilization. Journal of Applied Physiology 73, 1265–1272.CrossRefGoogle ScholarPubMed
Shindoh, C, Dimarco, A, Thomas, A, Manubay, P & Supinski, G (1990) Effect of N-acetylcysteine on diaphragm fatigue. Journal of Applied Physiology 68, 2107–2113.CrossRefGoogle ScholarPubMed
Starnes, J, Cantu, G, Farrar, R & Kehrer, JP (1989) Skeletal muscle lipid peroxidation in exercised and food-restricted rats during aging. Journal of Applied Physiology 67, 69–75.CrossRefGoogle ScholarPubMed
Tiidus, P & Houston, M (1993) Vitamin E status does not affect the responses to exercise training and acute exercise in female rats. Journal of Nutrition 123, 834–840.CrossRefGoogle Scholar
Vandenburgh, H (1992) Mechanical forces and their second messengers in stimulating cell growth in vitro. American Journal of Physiology 262, R350–R355.Google ScholarPubMed
Venditti, P & Di, Meo S (1996) Antioxidants, tissue damage, and endurance in trained and untrained young male rats. Archives of Biochemistry and Biophysics 331, 63–68.CrossRefGoogle ScholarPubMed
Venditti, P & Di, Meo S (1997) Effect of training on antioxidant capacity, tissue damage, and endurance of adult male rats. International Journal of Sports Medicine 18, 497–502.CrossRefGoogle ScholarPubMed
Vina, J, Sastre, J, Asensi, M & Packer, L (1995) Assay of blood glutathione oxidation during physical exercise. Methods in Enzymology 251, 237–243.CrossRefGoogle ScholarPubMed
Vincent, H, Powers, S, Demirel, H, Coombes, J & Naito, H (1999) Exercise training protects against contraction-induced lipid peroxidation in the diaphragm. European Journal of Applied Physiology 79, 268–273.CrossRefGoogle ScholarPubMed
Yu, B (1994) Cellular defenses against damage from reactive oxygen species. Physiological Reviews 74, 139–162.CrossRefGoogle ScholarPubMed