家族性和散发性肌萎缩性侧索硬化症的血超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性

Przedborski S. , Donaldson D.M. , Murphy P.L. , Hirsch O. , Lange D. , Naini A.B. , McKenna-Yasek D. , Brown, Jr R.H.
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引用次数: 57

摘要

最近的研究表明自由基与肌萎缩性侧索硬化症(ALS)的发病机制有关,ALS是一种致命的运动神经元麻痹性疾病。在这里,我们报告了三种主要自由基清除酶的红细胞活性测量:铜/锌超氧化物歧化酶(Cu/Zn-SOD),过氧化氢酶和谷胱甘肽过氧化物酶。我们研究了31例散发性ALS患者,18例家族性ALS患者和24例对照患者。8例Cu/Zn-SOD突变的家族性ALS患者的平均Cu/Zn-SOD活性降低,而未发现Cu/Zn-SOD突变的家族性ALS患者和散发性ALS患者的平均Cu/Zn-SOD活性正常。谷胱甘肽过氧化物酶活性仅在散发性ALS患者接受胰岛素样生长因子I (100 μg/kg)治疗时显著降低。散发性和家族性ALS患者过氧化氢酶活性正常。谷胱甘肽过氧化物酶和过氧化氢酶活性与症状持续时间或发病年龄均无显著相关性。维生素E、维生素C和β-胡萝卜素对三种酶的活性都没有影响。这些观察结果表明,过氧化氢酶和谷胱甘肽过氧化物酶功能的紊乱不太可能是ALS发病的中心因素。
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Blood Superoxide Dismutase, Catalase and Glutathione Peroxidase Activities in Familial and Sporadic Amyotrophic Lateral Sclerosis

Recent studies have implicated free radicals in the pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal, paralytic disorder of motor neurons. Herein we report on measurements of erythrocyte activity of the three main free radical scavenging enzymes: copper/zinc superoxide dismutase (Cu/Zn-SOD), catalase, and glutathione peroxidase. We studied 31 patients with sporadic ALS, 18 with familial ALS, and 24 controls, Mean Cu/Zn-SOD activity was reduced in eight familial ALS patients with mutations of Cu/Zn-SOD but was normal in patients with both familial ALS without identified Cu/Zn-SOD mutations and sporadic ALS. Glutathione peroxidase activity was significantly reduced only in sporadic ALS patients treated with insulin-like growth factor I (100 μg/kg). Catalase activity was normal in sporadic and familial ALS. Neither glutathione peroxidase nor catalase activities correlated significantly with duration of symptoms or age at onset. Vitamin E, vitamin C, and β-carotene did not affect any of the three enzyme activities. These observations indicate that disturbances of catalase and glutathione peroxidase function are not likely to be central factors in the pathogenesis of ALS.

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