Stacchiotti Alessandra, Rovetta Francesca, Ferroni Matteo, Corsetti Giovanni, Lavazza Antonio, Sberveglieri Giorgio, Aleo Maria Francesca
Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, Brescia University, Viale Europa 11, 25123 Brescia, Italy.
Department of Molecular and Translational Medicine, Brescia University, Viale Europa 11, 25123 Brescia, Italy.
Oxid Med Cell Longev. 2014;2014:840951. doi: 10.1155/2014/840951. Epub 2014 May 13.
Cisplatin (CisPt) is a widely used chemotherapeutic drug whose side effects include muscle weakness and cachexia. Here we analysed CisPt-induced atrophy in C2C12 myotubes by a multidisciplinary morphological approach, focusing on the onset and progression of autophagy, a protective cellular process that, when excessively activated, may trigger protein hypercatabolism and atrophy in skeletal muscle. To visualize autophagy we used confocal and transmission electron microscopy at different times of treatment and doses of CisPt. Moreover we evaluated the effects of taurine, a cytoprotective beta-amino acid able to counteract oxidative stress, apoptosis, and endoplasmic reticulum stress in different tissues and organs. Our microscopic results indicate that autophagy occurs very early in 50 μM CisPt challenged myotubes (4 h-8 h) before overt atrophy but it persists even at 24 h, when several autophagic vesicles, damaged mitochondria, and sarcoplasmic blebbings engulf the sarcoplasm. Differently, 25 mM taurine pretreatment rescues the majority of myotubes size upon 50 μM CisPt at 24 h. Taurine appears to counteract atrophy by restoring regular microtubular apparatus and mitochondria and reducing the overload and the localization of autophagolysosomes. Such a promising taurine action in preventing atrophy needs further molecular and biochemical studies to best define its impact on muscle homeostasis and the maintenance of an adequate skeletal mass in vivo.
顺铂（CisPt）是一种广泛使用的化疗药物，其副作用包括肌肉无力和恶病质。在这里，我们通过多学科形态学方法分析了顺铂诱导的C2C12肌管萎缩，重点关注自噬的发生和进展，自噬是一种保护性细胞过程，过度激活时可能引发骨骼肌中的蛋白质高分解代谢和萎缩。为了观察自噬，我们在不同的治疗时间和顺铂剂量下使用了共聚焦显微镜和透射电子显微镜。此外，我们评估了牛磺酸的作用，牛磺酸是一种具有细胞保护作用的β-氨基酸，能够对抗不同组织和器官中的氧化应激、细胞凋亡和内质网应激。我们的显微镜检查结果表明，在明显萎缩之前，50μM顺铂处理的肌管中自噬在很早的时候（4小时 - 8小时）就会发生，但即使在24小时时也会持续存在，此时几个自噬泡、受损的线粒体和肌浆泡沫会吞噬肌浆。不同的是，25mM牛磺酸预处理可在24小时时挽救50μM顺铂处理后的大多数肌管大小。牛磺酸似乎通过恢复正常的微管结构和线粒体，并减少自噬溶酶体的过载和定位来对抗萎缩。牛磺酸在预防萎缩方面如此有前景的作用需要进一步的分子和生化研究，以更好地确定其对肌肉稳态和体内适当骨骼肌质量维持的影响。
