Montesano Anna, Senesi Pamela, Luzi Livio, Benedini Stefano, Terruzzi Ileana
Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
Department of Biomedical Sciences for Health, University of Milan, Milan, Italy ; Metabolism Research Center, San Donato Hospital and Scientific Institute, Milan, Italy.
Oxid Med Cell Longev. 2015;2015:646171. doi: 10.1155/2015/646171. Epub 2015 Mar 8.
The targeting of nutraceutical treatment to skeletal muscle damage is an emerging area of research, driven by the need for new therapies for a range of muscle-associated diseases. L-Carnitine (CARN) is an essential nutrient and plays a key role in mitochondrial β-oxidation and in the ubiquitin-proteasome system regulation. As a dietary supplement to improve athletic performance, CARN has been studied for its potential to enhance β-oxidation. However, CARN effects on myogenesis, mitochondrial activity, and hypertrophy process are not completely elucidated. This in vitro study aims to investigate CARN role on skeletal muscle remodeling, differentiation process, and myotubes formation. We analyzed muscle differentiation and morphological features in C2C12 myoblasts exposed to 5 mM CARN. Our results showed that CARN was able to accelerate C2C12 myotubes formation and induce morphological changes, characterizing the start of hypertrophy process. In addition, CARN improved AKT activation and downstream cellular signaling pathways involved in skeletal muscle atrophy process prevention. Also, CARN positively regulated the pathways involved in oxidative stress defense. In this work, we provide an interesting novel mechanism of the potential therapeutic use of CARN to treat pathological conditions characterized by skeletal muscle morphological and functional impairment, oxidative stress production, and atrophy process in aging.
将营养保健品治疗靶向于骨骼肌损伤是一个新兴的研究领域,这是由一系列与肌肉相关疾病对新疗法的需求所驱动的。左旋肉碱(CARN)是一种必需营养素,在线粒体β-氧化和泛素-蛋白酶体系统调节中起关键作用。作为一种用于提高运动表现的膳食补充剂,人们已对CARN增强β-氧化的潜力进行了研究。然而,CARN对肌生成、线粒体活性和肥大过程的影响尚未完全阐明。这项体外研究旨在探讨CARN在骨骼肌重塑、分化过程和肌管形成中的作用。我们分析了暴露于5 mM CARN的C2C12成肌细胞中的肌肉分化和形态特征。我们的结果表明,CARN能够加速C2C12肌管的形成并诱导形态变化,这是肥大过程开始的特征。此外,CARN改善了AKT激活以及参与预防骨骼肌萎缩过程 的下游细胞信号通路。而且,CARN对参与氧化应激防御的通路具有正向调节作用。在这项工作中,我们提供了一种有趣的新机制,即CARN在治疗以骨骼肌形态和功能受损、氧化应激产生以及衰老过程中的萎缩为特征的病理状况方面的潜在治疗用途。