Progression of dystrophic features and activation of mitogen-activated protein kinases and calcineurin by physical exercise, in hearts of mdx mice.
We have previously demonstrated that calcineurin and p38 mitogen-activated protein kinase (MAPK) are up-regulated in the hearts of mdx mice. However, the degree of up-regulation observed was variable, which may reflect variable levels of daily physical activities among the mice. To investigate whether or not exercise affects dystrophic features and activates intracellular signaling molecules in mdx hearts, we subjected mdx and C57BL/10 mice to treadmill exercise and examined intracellular signaling molecules in cardiac muscles, at the protein level. The heart to body weight ratio was significantly increased in exercised mdx mice. Histopathology in exercised mdx hearts showed extensive infiltration of inflammatory cells, together with increases in interstitial fibrosis and adipose tissues, all of which were not observed either in exercised C57BL/10 or non-exercised mdx hearts. Phosphorylated p38 MAPK, phosphorylated extracellular signal-regulated kinase 1/2 and calcineurin, but not phosphorylated c-Jun N-terminal kinase 1, were up-regulated in exercised mdx hearts compared to exercised C57BL/10 or non-exercised mdx hearts. These data suggest that physical exercise accelerates the dystrophic process through activation of intracellular signaling molecules in dystrophin-deficient hearts.
Nakamura
Akinori
A
Third Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan. anakamu@hsp.md.shinshu-u.ac.jp
Yoshida
Kunihiro
K
Takeda
Shin'ichi
S
Dohi
Naoko
N
Ikeda
Shu-ichi
S
D000818:Animals; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D019703:Calcineurin / Q000378:metabolism*; D018450:Disease Progression; D004789:Enzyme Activation; D006352:Heart Ventricles / Q000201:enzymology / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D005082:Physical Exertion / Q000502:physiology*; D015854:Up-Regulation
D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin