Severe depletion of mitochondrial DNA in spinal muscular atrophy
Severe depletion of mitochondrial DNA in spinal muscular atrophy
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DOI：
10.1007/s00401-002-0638-1
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发表时间：
2003-03-01
影响因子：
12.7
通讯作者：
Sperl, W
中科院分区：
文献类型：
--
作者：
Berger, A;Mayr, JA;Sperl, W
脊髓性肌萎缩症（SMA）是一种儿童期神经肌肉疾病，导致肌肉力量急剧丧失。高分辨率极谱法和呼吸链酶测量的功能研究显示SMA患者肌肉组织的活动降低。为了更好地了解这种低能量供应，我们分析了20名遗传学证实的SMA无关儿童和31名对照儿童骨骼肌中线粒体DNA（mtDNA）的数量。定量Southern印迹分析显示，SMA患者肌肉mtDNA含量相对于核DNA（90.3 +/- 7.8%）有严重和均匀的减少，而免疫荧光法未检测到线粒体数量减少。此外，在SMA肌肉组织中检测到核编码复合物II（琥珀酸脱氢酶）活性降低2 - 3倍。蛋白质印迹分析表明，线粒体和核编码的细胞色素c氧化酶亚基显着减少。我们的研究结果表明，SMA的mtDNA耗竭是严重萎缩的结果，必须通过测量复合物II来区分与孤立的mtDNA减少，如发现在患者的巨噬细胞病变和所谓的mtDNA耗竭综合征。
Spinal muscular atrophy (SMA) is a neuromuscular disorder in childhood leading to a dramatic loss of muscle strength. Functional investigations with high-resolution polarography and enzyme measurements of the respiratory chain revealed lowered activities in muscle tissue of SMA patients. To gain a better understanding of this low energy supply we analyzed the amount of mitochondrial DNA (mtDNA) in skeletal muscle of 20 unrelated children with genetically proven SMA and 31 controls. Quantitative Southern blot analysis revealed a severe and homogeneous decrease in the content of muscle mtDNA in relation to nuclear DNA in SMA patients (90.3 +/- 7.8%), whereas by immunofluorescence no decrease in the number of mitochondria was detected. In addition, a two- to threefold reduction of the nuclear-encoded complex II (succinate dehydrogenase) activity was detected in SMA muscle tissue. Western blot analysis showed a significant reduction of both mitochondrial- and nuclear-encoded cytochrome c oxidase subunits. Our results indicate that mtDNA depletion in SMA is a consequence of severe atrophy, and has to be differentiated by measurement of complex II from an isolated reduction of mtDNA as found in patients with mitochondriocytopathies and the socalled mtDNA depletion syndrome.