Creatine supplementation reduces skeletal muscle degeneration and enhances mitochondrial function in mdx mice

被引:94
|
作者
Passaquin, AC
Renard, M
Kay, L
Challet, C
Mokhtarian, A
Wallimann, T
Ruegg, UT [1 ]
机构
[1] Univ Lausanne, Sch Pharm, Pharmacol Grp, CH-1015 Lausanne, Switzerland
[2] Swiss Fed Inst Technol, Inst Cell Biol, CH-8093 Zurich, Switzerland
基金
美国国家科学基金会;
关键词
calcium; creatine; creatine kinase; Duchenne muscular dystrophy; mdx mouse; mitochondria; muscle; muscular disease; permeability transition; respiration;
D O I
10.1016/S0960-8966(01)00273-5
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The mdx mouse serves as animal model for Duchenne muscular dystrophy. Energy status in muscles of mdx mice is impaired and we have demonstrated recently that the energy precursor creatine exerts beneficial effects on mdx skeletal muscle cells in culture. Here we show that feeding a creatine-enriched diet to new-born mdx mice strongly reduced the first wave of muscle necrosis four weeks after birth. Necrosis of the fast-twitch muscle extensor digitorum longus was inhibited by 63 +/- 14% (P<0.0001) while necrosis of the slow-switch soleus muscle was not significantly decreased. In addition, using chemically skinned muscle fibres,, we found that mitochondrial respiration capacity was decreased by about 25% in mdx-derived fibres and that long-term creatine-feeding restored respiration to wild, type levels. These results provide evidence that creatine supplementation in mdx mice improves muscle health and may provide a scientific basis for its use as adjuvant therapy in Duchenne muscular dystrophy. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:174 / 182
页数:9
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