Roses A D, Appel S H
Proc Natl Acad Sci U S A. 1973 Jun;70(6):1855-9. doi: 10.1073/pnas.70.6.1855.
Myotonic muscular dystrophy is a disorder of humans that involves many organ systems. Physiological studies have suggested that the fundamental defect is of membrane origin. Heretofore, no reproducible metabolic abnormalities have been demonstrated. In the present studies we used erythrocyte ghosts as a convenient source of purified membranes that do not possess changes of denervation, dystrophy, and fibrosis that might complicate the interpretation of muscle membrane changes. Our experiments demonstrated a significant difference in the phosphorylation of erythrocyte ghost protein by [gamma-(32)P]ATP, with endogenous protein kinase of erythrocyte membrane as the enzyme source. After ghosts were kept for 1 week at -20 degrees , phosphorylation of membrane protein in eight controls was twice as high as endogenous protein kinase activity measured in fresh preparations. No stimulation was seen in preparations from seven myotonic dystrophy patients from three different families. This reproducible difference in normal and myotonic membranes may represent an important new approach to studies of this debilitating inborn error of metabolism.
强直性肌营养不良是一种累及人体多个器官系统的疾病。生理学研究表明,其根本缺陷源于细胞膜。迄今为止,尚未证实存在可重复的代谢异常。在本研究中,我们使用红细胞血影作为纯化膜的便捷来源,这些膜不存在去神经、营养不良和纤维化等可能使肌肉膜变化的解释复杂化的改变。我们的实验表明,以红细胞膜内源性蛋白激酶作为酶源,用[γ-(32)P]ATP对红细胞血影蛋白进行磷酸化时存在显著差异。将血影在-20℃保存1周后,八个对照组中膜蛋白的磷酸化水平是新鲜制剂中测得的内源性蛋白激酶活性的两倍。来自三个不同家族的七名强直性肌营养不良患者的制剂中未观察到刺激现象。正常膜和强直性肌营养不良膜之间这种可重复的差异可能代表了研究这种使人衰弱的先天性代谢缺陷的一种重要新方法。