Role of oxidative damage in Friedreich's ataxia
Role of oxidative damage in Friedreich's ataxia
复制标题
DOI：
10.1023/b:nere.0000014826.00881.c3
复制
发表时间：
2004-03-01
影响因子：
4.4
通讯作者：
Cooper, JM
中科院分区：
文献类型：
--
作者：
Bradley, JL;Homayoun, S;Cooper, JM
弗里德赖希共济失调 (FRDA) 患者的血浆丙二醛 (MDA) 水平升高。这些水平与年龄和疾病持续时间的增加相关，表明脂质过氧化随着疾病进展而增加。使用 FRDA 患者的成纤维细胞，我们观察到 GSH 水平和乌头酸酶活性正常，表明他们的抗氧化状态没有变化。当接触各种增加自由基生成的物质时，我们观察到百草枯诱导的细胞内超氧化物生成导致氧化损伤增强。这与 GAA1 扩增的大小相关，表明 frataxin 水平降低可能使细胞更容易受到轻度氧化应激的影响。过氧化氢诱导的更严重的氧化应激导致 FRDA 成纤维细胞死亡增加，但与对照细胞没有显着差异。我们认为，异常的呼吸链功能和铁积累可能导致氧化损伤逐渐增加，但对自由基的敏感性增加可能不需要检测到呼吸链功能障碍。
Plasma malondialdehyde (MDA) levels were raised in Friedreich's ataxia ( FRDA) patients. These levels correlated with increasing age and disease duration, suggesting lipid peroxidation increased with disease progression. Using fibroblasts from FRDA patients we observed that GSH levels and aconitase activities were normal, suggesting their antioxidant status was unchanged. When exposed to various agents to increase free radical generation we observed that intracellular superoxide generation induced by paraquat caused enhanced oxidative damage. This correlated with the size of the GAA1 expansion, suggesting decreased frataxin levels may render the cells more vulnerable to mild oxidative stress. More severe oxidative stress induced by hydrogen peroxide caused increased cell death in FRDA fibroblasts but was not significantly different from control cells. We propose that abnormal respiratory chain function and iron accumulation may lead to a progressive increase in oxidative damage, but increased sensitivity to free radicals may not require detectable respiratory chain dysfunction.