Disabled early recruitment of antioxidant defenses in Friedreich's ataxia
Disabled early recruitment of antioxidant defenses in Friedreich's ataxia
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DOI：
10.1093/hmg/10.19.2061
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发表时间：
2001-09-15
影响因子：
3.5
通讯作者：
Rustin, P
中科院分区：
文献类型：
--
作者：
Chantrel-Groussard, K;Geromel, V;Rustin, P
弗里德赖希共济失调症（FRDA）是由线粒体铁超载引起的线粒体铁硫蛋白活性普遍缺乏引起的。然而，铁超载似乎是该疾病的晚期事件。本研究表明，与对照细胞相比，FRDA患者的成纤维细胞中的超氧化物歧化酶和进口铁机制都不是由内源性氧化应激诱导的。在条件frataxin-KO小鼠的心脏中，超氧化物歧化酶活性也未被诱导。这表明，由超氧化物歧化酶信号受阻导致的铁-硫簇的持续氧化损伤是FRDA中发生的线粒体缺乏和长期线粒体铁过载的原因。
Friedreich's ataxia (FRDA) results from a generalized deficiency of mitochondrial iron-sulfur protein activity ascribed to mitochondrial iron overload. However, iron overload appears to be a late event in the disease. Here we show that neither superoxide dismutases nor the import iron machinery was induced by an endogenous oxidative stress in FRDA patients' fibroblasts in contrast to control cells. Superoxide dismutase activity was not induced in the heart of conditional frataxin-KO mice either. This suggests that continuous oxidative damage to iron-ulfur clusters, resulting from hampered superoxide dismutase signaling, is causative of the mitochondrial deficiency and long term mitochondrial iron overload occurring in FRDA.