Wong A, Yang J, Danielson S, Gellera C, Taroni F, Cortopassi G
Department of Molecular Biosciences, University of California, Davis 95616, USA.
Antioxid Redox Signal. 2000 Fall;2(3):461-5. doi: 10.1089/15230860050192233.
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease resulting from decreased expression of the nuclear-encoded mitochondrial protein, frataxin. FRDA patients have characteristic iron deposits and dysfunction of mitochondrial enzymes in the heart. Inactivation of the frataxin homologue in yeast causes dysregulation of both mitochondrial iron levels and iron export. Previously, we have observed sensitivity of FRDA fibroblasts to FeCl3 and hydrogen peroxide, results consistent with the hypothesis that FRDA cells may experience increased Fenton chemistry. To determine whether the sensitivity of FRDA cells to transition metal ions is a general or specific property, we have compared the sensitivity of lymphoblasts from FRDA patients and healthy controls to the transition metal salts CoCl2, CuSO4 FeCl3 FeSO4, MnCl2, and ZnCl2. FRDA lymphoblasts were significantly more sensitive to FeCl3 and MnCl2 than control cells. However, there were no significant differences observed in sensitivity to CoCl2, CuSO4, FeSO4 and ZnCl2 in the concentration ranges studied. Thus, the sensitivity of FRDA lymphoblasts exposed to transition metals appears to be specific, and could be relevant to the pathophysiological mechanism, which is discussed.
弗里德赖希共济失调（FRDA）是一种常染色体隐性神经退行性疾病，由核编码的线粒体蛋白——酵母铁蛋白的表达减少所致。FRDA患者心脏中有特征性的铁沉积以及线粒体酶功能障碍。酵母中铁蛋白同源物的失活会导致线粒体铁水平和铁输出的失调。此前，我们观察到FRDA成纤维细胞对FeCl3和过氧化氢敏感，这一结果与FRDA细胞可能经历增强的芬顿化学反应这一假说相符。为了确定FRDA细胞对过渡金属离子的敏感性是一种普遍特性还是特定特性，我们比较了FRDA患者和健康对照者的淋巴细胞对过渡金属盐CoCl2、CuSO4、FeCl3、FeSO4、MnCl2和ZnCl2的敏感性。FRDA淋巴细胞对FeCl3和MnCl2的敏感性显著高于对照细胞。然而，在所研究的浓度范围内，对CoCl2、CuSO4、FeSO4和ZnCl2的敏感性未观察到显著差异。因此，暴露于过渡金属的FRDA淋巴细胞的敏感性似乎是特定的，并且可能与所讨论的病理生理机制相关。
