Disatnik M H, Chamberlain J S, Rando T A
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Room A343, Stanford, California 94305-5235, USA.
Muscle Nerve. 2000 May;23(5):784-92. doi: 10.1002/(sici)1097-4598(200005)23:5<784::aid-mus17>3.0.co;2-y.
Mutations in the dystrophin gene that lead to the expression of truncated forms of the dystrophin protein cause muscular dystrophies of varying severities both in humans and in mice. We have shown previously that dystrophin-deficient muscle is more susceptible to oxidative injury than is normal muscle. In this report, we have used muscle cells derived from mdx mice, which express no dystrophin, and mdx-transgenic strains that express full-length dystrophin or truncated forms of dystrophin to explore further the relationship between dystrophin expression and susceptibility of muscle to oxidative injury. We show that, when differentiated into myotubes, the relative susceptibility of the cell populations to oxidative stress correlates with the severity of the dystrophy in the strain from which the cells were isolated. The most susceptible populations exhibited the greatest oxidative damage as assessed by protein oxidation. Thus, the relative efficacy of truncated dystrophin proteins to protect muscle from necrotic degeneration in vivo is predicted by their ability to protect muscle cells from free radical mediated injury. These findings support the hypothesis that the dystrophin protein complex may have important regulatory or signaling properties in terms of cell survival and antioxidant defense mechanisms.
肌营养不良蛋白基因的突变会导致截短形式的肌营养不良蛋白表达，从而在人类和小鼠中引发不同严重程度的肌肉营养不良症。我们之前已经表明，缺乏肌营养不良蛋白的肌肉比正常肌肉更容易受到氧化损伤。在本报告中，我们使用了来自mdx小鼠（不表达肌营养不良蛋白）以及表达全长或截短形式肌营养不良蛋白的mdx转基因品系的肌肉细胞，进一步探究肌营养不良蛋白表达与肌肉对氧化损伤易感性之间的关系。我们发现，当分化为肌管时，细胞群体对氧化应激的相对易感性与分离这些细胞的品系中肌肉营养不良症的严重程度相关。通过蛋白质氧化评估，最易感的群体表现出最大程度的氧化损伤。因此，截短的肌营养不良蛋白在体内保护肌肉免于坏死性退变的相对效力，可通过其保护肌肉细胞免受自由基介导损伤的能力来预测。这些发现支持了这样一种假说，即就细胞存活和抗氧化防御机制而言，肌营养不良蛋白复合物可能具有重要的调节或信号传导特性。
