研究发现肌肉萎缩症患者心脏衰竭的原因

近日，西澳大利亚大学研究人员首次发现了肌细胞膜钙通道与线粒体功能之间的通信故障可能是造成肌肉萎缩症患者心脏衰竭的原因。这项研究显示，缺乏抗肌萎缩蛋白小鼠的肌细胞膜钙通道线粒体功能之间的通信受损。

目前，肌肉萎缩症患者心脏衰竭机制不明，另据此前报道，缺乏抗肌萎缩蛋白(负责肌肉萎缩症)会改变钙离子通道的功能。在最新研究中，研究人员已经确定了通道和线粒体之间的联系。

在肌营养不良症中，膜钙通道和线粒体之间的功能“通信”受到损害。我们曾表明L-型钙通道在心脏中可能改变代谢活动，主要作者Livia Hool教授解释：L-型钙通道被普遍认为在调节心脏跳动和收缩中是重要的，我们已经证明了通道在调节代谢活动中的额外作用。这项研究表明，当抗肌萎缩蛋白缺失，细胞结构“乱了阵脚”，钙通道和线粒体之间的沟通变得混乱导致心脏衰竭。

这是一个重要的发现，因为它提供了肌营养不良症心脏衰竭的一种机制，此外，研究已经证明，给予小鼠啉寡聚肽治疗能诱导抗肌萎缩蛋白的功能性表达，挽救老鼠代谢活动。研究也对于理解其他类型的心脏衰竭机制有显著影响。

链接

NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function

Hiroyasu Yamamoto, Evan G. Williams, Laurent Mouchiroud, Carles Cantó, Weiwei Fan, Michael Downes, Christophe Héligon, Grant D. Barish, Béatrice Desvergne, Ronald M. Evans et al.

Transcriptional coregulators control the activity of many transcription factors and are thought to have wide-ranging effects on gene expression patterns. We show here that muscle-specific loss of nuclear receptor corepressor 1 (NCoR1) in mice leads to enhanced exercise endurance due to an increase of both muscle mass and of mitochondrial number and activity. The activation of selected transcription factors that control muscle function, such as MEF2, PPARβ/, and ERRs, underpins these phenotypic alterations. NCoR1 levels are decreased in conditions that require fat oxidation, resetting transcriptional programs to boost oxidative metabolism. Knockdown of gei-8, the sole C. elegans NCoR homolog, also robustly increased muscle mitochondria and respiration, suggesting conservation of NCoR1 function. Collectively, our data suggest that NCoR1 plays an adaptive role in muscle physiology and that interference with NCoR1 action could be used to improve muscle function.