Fontes-Oliveira Cibely Cristine, Busquets Sílvia, Toledo Míriam, Penna Fabio, Paz Aylwin Maria, Sirisi Sònia, Silva Ana Paula, Orpí Marcel, García Albert, Sette Angelica, Inês Genovese Maria, Olivan Mireia, López-Soriano Francisco J, Argilés Josep M
Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645 08028-Barcelona, Spain.
Biochim Biophys Acta. 2013 Mar;1830(3):2770-8. doi: 10.1016/j.bbagen.2012.11.009.
Cachexia is a wasting condition that manifests in several types of cancer, and the main characteristic is the profound loss of muscle mass.
The Yoshida AH-130 tumor model has been used and the samples have been analyzed using transmission electronic microscopy, real-time PCR and Western blot techniques.
Using in vivo cancer cachectic model in rats, here we show that skeletal muscle loss is accompanied by fiber morphologic alterations such as mitochondrial disruption, dilatation of sarcoplasmic reticulum and apoptotic nuclei. Analyzing the expression of some factors related to proteolytic and thermogenic processes, we observed in tumor-bearing animals an increased expression of genes involved in proteolysis such as ubiquitin ligases Muscle Ring Finger 1 (MuRF-1) and Muscle Atrophy F-box protein (MAFBx). Moreover, an overexpression of both sarco/endoplasmic Ca(2+)-ATPase (SERCA1) and adenine nucleotide translocator (ANT1), both factors related to cellular energetic efficiency, was observed. Tumor burden also leads to a marked decreased in muscle ATP content.
In addition to muscle proteolysis, other ATP-related pathways may have a key role in muscle wasting, both directly by increasing energetic inefficiency, and indirectly, by affecting the sarcoplasmic reticulum-mitochondrial assembly that is essential for muscle function and homeostasis.
The present study reports profound morphological changes in cancer cachectic muscle, which are visualized mainly in alterations in sarcoplasmic reticulum and mitochondria. These alterations are linked to pathways that can account for energy inefficiency associated with cancer cachexia.
恶病质是一种在多种癌症中出现的消耗性病症，其主要特征是肌肉量严重减少。
使用吉田AH - 130肿瘤模型，并采用透射电子显微镜、实时聚合酶链反应和蛋白质免疫印迹技术对样本进行分析。
通过使用大鼠体内癌症恶病质模型，我们在此表明骨骼肌损失伴随着纤维形态学改变，如线粒体破坏、肌浆网扩张和凋亡细胞核。在分析与蛋白水解和产热过程相关的一些因子的表达时，我们在荷瘤动物中观察到参与蛋白水解的基因如泛素连接酶肌肉环指蛋白1（MuRF - 1）和肌肉萎缩F盒蛋白（MAFBx）的表达增加。此外，还观察到肌浆/内质网Ca(2 +) - ATP酶（SERCA1）和腺嘌呤核苷酸转位酶（ANT1）这两个与细胞能量效率相关的因子均有过表达。肿瘤负荷还导致肌肉ATP含量显著降低。
除了肌肉蛋白水解外，其他与ATP相关的途径可能在肌肉消耗中起关键作用，既直接通过增加能量低效，又间接通过影响对肌肉功能和内环境稳定至关重要的肌浆网 - 线粒体装配。
本研究报告了癌症恶病质肌肉中深刻的形态学变化，主要表现为肌浆网和线粒体的改变。这些改变与可解释与癌症恶病质相关的能量低效的途径有关。
