Increased levels of adenine nucleotide translocator 1 protein and response to oxidative stress are early events in facioscapulohumeral muscular dystrophy muscle
Increased levels of adenine nucleotide translocator 1 protein and response to oxidative stress are early events in facioscapulohumeral muscular dystrophy muscle
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DOI：
10.1007/s00109-004-0583-7
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发表时间：
2005-03-01
影响因子：
4.7
通讯作者：
Fernandez, A
中科院分区：
文献类型：
--
作者：
Laoudj-Chenivesse, D;Carnac, G;Fernandez, A
面肩肱骨肌营养不良症（FSHD）是一种常染色体显性神经肌肉疾病，与染色体4q35上串联排列的3.3 kb重复序列（D4Z4）缺失有因果关系。尽管有报道称一些4q35基因的表达增加，但最近的两项研究反驳了这一观点，发现任何4q35基因的转录水平都没有显著变化，其中包括腺嘌呤核苷酸转位子（ANTI）的心脏和肌肉特异性异构体。我们发现，与控制健康肌肉相比，未受影响和受影响的FSHD肌肉中的抗蛋白水平均显着增加。在健康、杜氏肌营养不良和FSHD肌肉之间的蛋白质表达比较分析表明，参与线粒体功能和氧化应激保护的蛋白质在所有FSHD肌肉中也可重复和特异性修饰，包括临床未受影响的肌肉。因此，ANTI表达增加和线粒体功能障碍可能是FSHD发病机制的初始事件，并代表潜在的治疗靶点。
Facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant neuromuscular disorder, has been causally related to deletion of tandemly arrayed 3.3 kb repeats (D4Z4) on chromosome 4q35. Although increased expression of several 4q35 genes has been reported, two recent studies dispute this, finding no significant changes in the transcriptional level of any of the 4q35 genes, among which is the heart and muscle-specific isoform of the adenine nucleotide translocator (ANTI). We found markedly increased levels of ANTI protein in both unaffected and affected FSHD muscles in comparison to control healthy muscles. Comparative protein expression analysis between healthy, Duchenne muscular dystrophy, and FSHD muscle shows that proteins involved in mitochondrial function and protection from oxidative stress are also reproducibly and specifically modified in all FSHD muscles, including clinically unaffected muscles. Increased ANTI expression and mitochondrial dysfunction may thus be initial events in FSHD pathogenesis and represent potential therapeutic targets.