Effects of exercise and steroid on skeletal muscle apoptosis in the mdx mouse
Jeong-Hoon Lim MD
Department of Rehabilitation Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Republic of Korea
Search for more papers by this authorDai-Youl Kim MD
Department of Rehabilitation Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Republic of Korea
Search for more papers by this authorCorresponding Author
Moon Suk Bang MD, PhD
Department of Rehabilitation Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Republic of Korea
Department of Rehabilitation Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Republic of KoreaSearch for more papers by this authorJeong-Hoon Lim MD
Department of Rehabilitation Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Republic of Korea
Search for more papers by this authorDai-Youl Kim MD
Department of Rehabilitation Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Republic of Korea
Search for more papers by this authorCorresponding Author
Moon Suk Bang MD, PhD
Department of Rehabilitation Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Republic of Korea
Department of Rehabilitation Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, Seoul 110-744, Republic of KoreaSearch for more papers by this authorAbstract
Reports concerning the influence of exercise loading and steroid administration on dystrophinopathy are inconsistent. To investigate the effect of muscle exercise in Duchenne muscular dystrophy (DMD), 15 control and 15 mdx mice, an animal model of DMD, were divided into free-living (n = 6), exercise (n = 6), and immobilization (n = 3) groups. Free-living and exercise groups were further divided into steroid-treated and sham-treated groups to evaluate the effect of steroid administration. We measured apoptotic changes by in situ DNA nick-end labeling (TUNEL), DNA fragmentation assay, and Western blotting for Bcl-2 and BAX. Apoptosis was most prominent in the sham-treated exercise group, and it was significantly reduced in the steroid-treated exercise group. The steroid-treated free-living group showed a higher rate of apoptotic change than the sham-treated free-living group. Apoptosis was minimized in the free-living condition, whereas exercise loading and immobilization caused apoptotic change in this muscular dystrophy animal model. Steroid administration induced apoptosis in muscle of free-living mice, but alleviated the apoptotic damage caused by exercise loading in mdx mice. These findings suggest that steroid administration may be effective in preventing a postexercise deterioration of skeletal muscle in animal models of DMD. Muscle Nerve 30: 456–462 2004
REFERENCES
- 1 Adams V, Gielen S, Hambrecht R, Schuler G. Apoptosis in skeletal muscle. Front Biosci 2001; 6: D1–D11.
- 2 Anderson JE, Vargas C. Correlated NOS-Iμ and myf5 expression by satellite cells in mdx mouse muscle regeneration during NOS manipulation and deflazacort treatment. Neuromuscul Disord 2003; 13: 388–396.
- 3 Bejma J, Ji LL. Aging and acute exercise enhance free radical generation in rat skeletal muscle. J Appl Physiol 1999; 87: 465–470.
- 4 Bradford MM. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–254.
- 5 Disatnik MH, Dhawan J, Yu Y, Beal MF, Whirl MM, Franco AA, Rando TA. Evidence of oxidative stress in mdx mouse muscle: Studies of the pre-necrotic state. J Neurol Sci 1998; 161: 77–84.
- 6Dupont- Versteegden EE, McCarter RJ, Katz MS. Voluntary exercise decreases progression of muscular dystrophy in diaphragm of mdx mice. J Appl Physiol 1994; 77: 1736–1741.
- 7 Gal I, Varga T, Szilagyi I, Balazs M, Schlammadinger J, Szabo G Jr. Protease-elicited TUNEL positivity of non-apoptotic fixed cells. J Histochem Cytochem 2000; 48: 963–970.
- 8 Gama P, Goldfeder EM, de Moraes JC, Alvares EP. Cell proliferation and death in the bastric epithelium of developing rat after glucocorticoid treatments. Anat Rec 2000; 260: 213–221.
- 9 Green DR, Reed JC. Mitochondria and apoptosis. Science 1998; 281: 1309–1312.
- 10 Hatanaka K, Ikegaya H, Takase I, Kobayashi M, Iwase H, Yoshida K. Immobilization stress-induced thymocyte apoptosis in rats. Life Sci 2001; 69: 155–165.
- 11 Han S, Choi H, Ko MG, Choi YI, Sohn DH, Kim JK, Shin D, Chung H, Lee HW, Kim JB, Park SD, Seong RH. Peripheral T cells become sensitive to glucocorticoid- and stress-induced apoptosis in transgenic mice overexpressing SRG3. J Immunol 2001; 167: 805–810.
- 12 Hegardt C, Andersson G, Oredsson SM. Spermine prevents cytochrome c release in glucocorticoid-induced apoptosis in mouse thymocytes. Cell Biol Int 2003; 27: 115–121.
- 13 Hoffman EP, Brown RH Jr, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 1987; 51; 919–928.
- 14 Ji LL. Antioxidant enzyme response to exercise and aging. Med Sci Sports Exerc 1993; 25: 225–231.
- 15 Luo G, Sun X, Hungness E, Hasselgren PO. Heat shock protects L6 myotubes from catabolic effects of dexamethasone and prevents downregulation of NF-kappaB. Am J Physiol Regul Integr Comp Physiol 2001; 281: R1193–R1200.
- 16 Melcangi RC, Cavarretta I, Magnaghi V, Ciusani E, Salmaggi A. Corticosteroids protect oligodendrocytes from cytokine-induced cell death. Neuroreport 2000; 11: 3969–3972.
- 17 Mignotte B, Vayssiere JL. Mitochondria and apoptosis. Eur J Biochem 1998; 252: 1–15.
- 18 Musacchia XJ, Deavers DR, Meininger GA, Davis TP. A model for hypokinesia: effects on muscle atrophy in the rat. J Appl Physiol 1980; 48: 479–486.
- 19 Ohyama K, Oka K, Emura A, Tamura H, Suga T, Bessho T, Hirakawa S, Yamakawa T. Suppression of apoptotic cell death progressed in vitro with incubation of the chorion laeve tissues of human fetal membrane by glucocorticoid. Biol Pharm Bull 1998; 21: 1024–1029.
- 20 Puviani M, Marconi A, Cozzani E, Pincelli C. Fas ligand in pemphigus sera induces keratinocyte apoptosis through the activation of caspase-8. J Invest Dermatol 2003; 120: 164–167.
- 21 Radak Z, Asano K, Inoue M, Kizaki T, Oh-Ishi S, Suzuki K, Taniguchi N, Ohno H. Superoxide dismutase derivative reduces oxidative damage in skeletal muscle of rats during exhaustive exercise. J Appl Physiol 1995; 79: 129–135.
- 22 Sasagawa I, Yazawa H, Suzuki Y, Nakada T. Stress and testicular germ cell apoptosis. Arch Androl 2001; 47: 211–216.
- 23 Sandri M, Carraro U, Podhorska-Okolov M, Rizzi C, Arslan P, Monti D, Franceschi C. Apoptosis, DNA damage and ubiquitin expression in normal and mdx muscle fibers after exercise. FEBS Lett 1995; 373: 291–295.
- 24 Singleton JR, Baker BL, Thorburn A. Dexamethasone inhibits insulin-like growth factor signaling and potentiates myoblast apoptosis. Endocrinology 2000; 141: 2945–2950.
- 25 Smith HK, Maxwell L, Martyn JA, Bass JJ. Nuclear DNA fragmentation and morphological alterations in adult rabbit skeletal muscle after short-term immobilization. Cell Tissue Res 2000; 302: 235–241.
- 26 Stadelmann C, Lassmann H. Detection of apoptosis in tissue sections. Cell Tissue Res 2000; 301: 19–31.
- 27 Stupka N, Lowther S, Chorneyko K, Bourgeois JM, Hogben C, Tarnopolsky MA. Gender differences in muscle inflammation after eccentric exercise. J Appl Physiol 2000; 89: 2325–2332.
- 28 Suzuki K, Smolenski RT, Jayakumar J, Murtuza B, Brand NJ, Yacoub MH. Heat shock treatment enhances graft cell survival in skeletal myoblast transplantation to the heart. Circulation 2000; 102: III216–III221.
- 29 Tews DS. Apoptosis and muscle fibre loss in neuromuscular disorders. Neuromuscul Disord 2002; 12: 613–622.
- 30 Tiball JG, Albrecht DE, Lokensgard BE, Spencer MJ. Apoptosis precedes necrosis of dystrophin-deficient muscle. J Cell Sci 1995; 108: 2197–2204.
- 31 Tonomura N, McLaughlin K, Grimm L, Goldsby RA, Osborne BA. Glucocorticoid-induced apoptosis of thymocytes: requirement of proteasome-dependent mitochondrial activity. J Immunol 2003; 170: 2469–2478.
- 32 Webster JC, Huber RM, Hanson RL, Collier PM, Haws TF, Mills JK, Burn TC, Allegretto EA. Dexamethasone and tumor necrosis factor-alpha act together to induce the cellular inhibitor of apoptosis-2 gene and prevent apoptosis in a variety of cell types. Endocrinology 2002; 143: 3866–3874.
- 33 Wong BL, Christopher C. Corticosteroids in Duchenne muscular dystrophy: a reappraisal. J Child Neurol 2002; 17: 183–190.
- 34
Zaugg M,
Jamali NZ,
Lucchinetti E,
Xu W,
Alam M,
Shafiq SA,
Siddiqui MA.
Anabolic-androgenic steroids induce apoptotic cell death in adult rat ventricular myocytes.
J Cell Physiol
2001;
187:
90–95.
10.1002/1097-4652(2001)9999:9999<00::AID-JCP1057>3.0.CO;2-Y CAS PubMed Web of Science® Google Scholar