Effects of exercise and steroid on skeletal muscle apoptosis in the mdx mouse.
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.
Lim
Jeong-Hoon
JH
Department of Rehabilitation Medicine, Seoul National University College of Medicine, 28 Yongon-dong Chongno-gu, 110-744, Republic of Korea.
Kim
Dai-Youl
DY
Bang
Moon Suk
MS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002875:Chromosomes / Q000737:chemistry / Q000235:genetics; D019938:Cyclin D1 / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000235:genetics; D053938:DNA Fragmentation; D004591:Electrophoresis, Polyacrylamide Gel; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000166:cytology* / Q000187:drug effects; D005082:Physical Exertion / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D013256:Steroids / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D013256:Steroids; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D004247:DNA