A

Scientifiques DE L’É.N.S, B. Gambier, Normale Supérieure
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Abstract

Background: The potassium channel encoded by the ether-a-gogo-related gene 1A (erg1a) has been detected in the atrophying skeletal muscle of mice experiencing either muscle disuse or cancer cachexia and further evidenced to contribute to muscle deterioration by enhancing ubiquitin proteolysis; however, to our knowledge, ERG1A has not been reported in human skeletal muscle. Methods and Results: Here, using immunohistochemistry, we detect ERG1A immunofluorescence in human Rectus abdominis skeletal muscle sarcolemma. Further, using single point brightness data, we report the detection of ERG1A immunofluorescence at low levels in the Rectus abdominis muscle sarcolemma of young adult humans and show that it trends toward greater levels (10.6%) in healthy aged adults. Interestingly, we detect ERG1A immunofluorescence at a statistically greater level (53.6%; p < 0.05) in the skeletal muscle of older cancer patients than in age-matched healthy adults. Importantly, using immunoblot, we reveal that lower mass ERG1A protein is 61.5% (p < 0.05) more abundant in the skeletal muscle of cachectic older adults than in healthy age-matched controls. Additionally, we report that the ERG1A protein is detected in a cultured human rhabdomyosarcoma line that may be a good in vitro model for the study of ERG1A in muscle. Conclusions: The data demonstrate that ERG1A is detected more abundantly in the atrophied skeletal muscle of cancer patients, suggesting it may be related to muscle loss in humans as it has been shown to be in mice experiencing muscle atrophy as a result of malignant tumors.
一个
背景:在经历肌肉失用或癌症恶病质的小鼠的萎缩骨骼肌中,已经检测到由醚a-gogo相关基因1A (erg1a)编码的钾通道,并进一步证明通过增强泛素蛋白水解促进肌肉退化;然而,据我们所知,ERG1A尚未在人类骨骼肌中报道。方法和结果:本研究采用免疫组化方法检测人腹直肌骨骼肌肌膜中ERG1A的免疫荧光。此外,利用单点亮度数据,我们报告了在年轻人腹直肌肌膜中检测到低水平的ERG1A免疫荧光,并显示其在健康老年人中呈更高水平(10.6%)的趋势。有趣的是,我们检测到的ERG1A免疫荧光水平在统计学上更高(53.6%;P < 0.05),老年癌症患者的骨骼肌比同龄健康成人的骨骼肌含量高。重要的是,通过免疫印迹,我们发现低质量ERG1A蛋白在恶病质老年人骨骼肌中的含量比健康年龄匹配的对照组高61.5% (p < 0.05)。此外,我们报道在培养的人横纹肌肉瘤细胞系中检测到ERG1A蛋白,这可能是研究肌肉中ERG1A的良好体外模型。结论:数据表明,ERG1A在癌症患者萎缩的骨骼肌中检测到的含量更高,这表明它可能与人类肌肉损失有关,因为它已被证明与恶性肿瘤引起的肌肉萎缩的小鼠有关。
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