Overexpression of the mitochondrial T3 receptor induces skeletal muscle atrophy during aging.
Overexpression of the mitochondrial T3 receptor induces skeletal muscle atrophy during aging.
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DOI：
10.1371/journal.pone.0005631
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发表时间：
2009-05-20
期刊：
影响因子：
3.7
通讯作者：
Wrutniak-Cabello C
中科院分区：
文献类型：
--
作者：
Casas F;Pessemesse L;Grandemange S;Seyer P;Baris O;Gueguen N;Ramonatxo C;Perrin F;Fouret G;Lepourry L;Cabello G;Wrutniak-Cabello C
在以前的研究中，我们的特点是一个新的激素途径，涉及线粒体T3受体（p43）作为线粒体转录因子。在体外和体内研究中，我们已经表明，p43增加线粒体转录和线粒体生物合成。此外，骨骼肌中p43过表达刺激线粒体呼吸，并诱导肌纤维代谢和收缩特征的转变，其变得更加氧化。在这里，我们研究了p43过表达在小鼠骨骼肌衰老过程中的影响。我们报告说，p43过度表达最初增加线粒体质量。然而，在转基因小鼠2月龄时线粒体DNA含量出现早期上升后，我们观察到线粒体DNA含量逐渐下降，在23月龄时相对于对照动物降低了2倍。此外，p43过表达诱导的氧化应激，其特征在于在四头肌的脂质过氧化和蛋白质氧化的强烈增加，虽然抗氧化酶活性（过氧化氢酶和超氧化物歧化酶）的刺激。此外，肌肉萎缩在6月龄时变得可检测，可能是通过两种肌肉特异性泛素连接酶E3，Atrogin-1/MAFbx和MuRF 1刺激泛素蛋白酶体途径。总之，这些结果表明，线粒体活性的长期刺激诱导肌肉萎缩。此外，这些数据强调了严格控制p43表达的重要性，并表明直接T3线粒体途径的失调可能是参与肌肉减少症发生的参数之一。
In previous studies, we characterized a new hormonal pathway involving a mitochondrial T3 receptor (p43) acting as a mitochondrial transcription factor. In in vitro and in vivo studies, we have shown that p43 increases mitochondrial transcription and mitochondrial biogenesis. In addition, p43 overexpression in skeletal muscle stimulates mitochondrial respiration and induces a shift in metabolic and contractile features of muscle fibers which became more oxidative. Here we have studied the influence of p43 overexpression in skeletal muscle of mice during aging. We report that p43 overexpression initially increased mitochondrial mass. However, after the early rise in mitochondrial DNA occurring at 2 months of age in transgenic mice, we observed a progressive decrease of mitochondrial DNA content which became 2-fold lower at 23 months of age relatively to control animals. Moreover, p43 overexpression induced an oxidative stress characterized by a strong increase of lipid peroxidation and protein oxidation in quadriceps muscle, although antioxidant enzyme activities (catalase and superoxide dismutase) were stimulated. In addition, muscle atrophy became detectable at 6 months of age, probably through a stimulation of the ubiquitin proteasome pathway via two muscle-specific ubiquitin ligases E3, Atrogin-1/MAFbx and MuRF1. Taken together, these results demonstrate that a prolonged stimulation of mitochondrial activity induces muscle atrophy. In addition, these data underline the importance of a tight control of p43 expression and suggest that a deregulation of the direct T3 mitochondrial pathway could be one of the parameters involved in the occurrence of sarcopenia.
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影响因子：
3.5
作者：
Busquets, S;Almendro, V;López-Soriano, FJ
通讯作者：
López-Soriano, FJ
影响因子：
2.7
作者：
Lynch, GS;Hinkle, RT;Faulkner, JA
通讯作者：
Faulkner, JA
影响因子：
4.8
作者：
Rochard, P;Rodier, A;Cabello, G
通讯作者：
Cabello, G
DOI：
10.1016/s0006-291x(02)00355-8
发表时间：
2002-05-17
影响因子：
3.1
作者：
Argilés, JM;Busquets, S;López-Soriano, FJ
通讯作者：
López-Soriano, FJ
DOI：
10.1083/jcb.200108089
发表时间：
2002-04-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
McElhinny AS;Kakinuma K;Sorimachi H;Labeit S;Gregorio CC
通讯作者：
Gregorio CC