Progression of dystrophic features and activation of mitogen‐activated protein kinases and calcineurin by physical exercise, in hearts of mdx mice

FEBS Letters

Dohi, Naoko³  Ikeda, Shu-ichi³  Takeda, Shin'ichi²  Nakamura, Akinori³  Yoshida, Kunihiro¹ 

[1] Division of Clinical and Molecular Genetics, Shinshu University Hospital, 3-1-1 Asahi, Matsumoto 390-8621, Japan;Department of Molecular Therapy, National Institute of Neruroscience, NCNP, 4-1-1 Ogawahigashi-Cho, Kodaira, Tokyo 187-8502, Japan;Third Department of Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan

关键词: Dystrophin-deficient heart;    Exercise;    p38 mitogen-activated protein kinase;    c-Jun N-terminal kinase 1;    Extracellular signal-regulated kinase 1/2;    Calcineurin;   

DOI  :  10.1016/S0014-5793(02)02739-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown