Leucine modulates the effect of Walker factor, a proteolysis-inducing factor-like protein from Walker tumours, on gene expression and cellular activity in C2C12 myotubes
Leucine modulates the effect of Walker factor, a proteolysis-inducing factor-like protein from Walker tumours, on gene expression and cellular activity in C2C12 myotubes
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DOI：
10.1016/j.cyto.2013.05.018
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发表时间：
2013-10-01
期刊：
影响因子：
3.8
通讯作者：
Cintra Gomes-Marcondes, Maria Cristina
中科院分区：
文献类型：
--
作者：
Goncalves, Estela Maria;Salomao, Emilianne Miguel;Cintra Gomes-Marcondes, Maria Cristina
癌症恶病质导致严重的体重减轻，特别是骨骼肌的消耗，这是由于蛋白质catenin增加和/或蛋白质合成减少而发生的。在癌症患者中观察到的肌肉蛋白质降解由肿瘤产生的特定细胞因子蛋白水解诱导因子（PIF）介导。这种蛋白质增加了泛素-蛋白酶体途径的活性，这些患者的肌肉蛋白质合成可能受到几种因素的影响，包括营养相关的信号传导。某些营养素，如亮氨酸，可降低恶病质动物的泛素-蛋白酶体途径活性，增加骨骼肌蛋白质含量。在这项研究中，我们研究了亮氨酸对细胞活力，形态，功能蛋白酶体活性，酶活性，蛋白质合成和降解暴露于蛋白水解诱导因子（PIF）样蛋白纯化的步行者荷瘤大鼠C2 C12肌管的影响。步行者因子（WF）对肌管细胞无细胞毒性作用，WF和/或亮氨酸存在时，其形态特征未发生改变。然而，观察到碱性磷酸酶活性增加。在较高的WE浓度下，糜蛋白酶样活性、组织蛋白酶B活性和20 S蛋白酶体基因表达增加。在暴露于WF之前用亮氨酸处理肌管导致蛋白酶体活性以及胰凝乳蛋白酶和组织蛋白酶的活性降低。总蛋白质合成下降，WF处理的细胞伴随着蛋白质降解增加。亮氨酸暴露后，观察到的WF的影响是最小的，甚至在某些情况下恢复。两者合计，这些结果表明亮氨酸对WF在C2 C12肌管细胞中的作用具有重要的调节作用。(C)2013爱思唯尔有限公司保留所有权利。
Cancer-cachexia causes severe weight loss, particularly from the wasting of skeletal muscle, which occurs due to increased protein catabolism and/or decreased protein synthesis. The muscle protein degradation observed in cancer patients is mediated by a specific cytokine, proteolysis-inducing factor (PIF), which is produced by the tumour. This protein increases the ubiquitin-proteasome pathway activity, and the synthesis of muscle protein in these patients can be affected by several factors, including nutrient-related signalling. Some nutrients, such as leucine, can decrease the ubiquitin-proteasome pathway activity and increase the skeletal muscle protein content in cachectic animals. In this study, we investigated the effects of leucine on cell viability, morphology, functional proteasome activity, enzymatic activity, and protein synthesis and degradation in C2C12 myotubes exposed to the proteolysis-inducing factor (PIF)-like protein purified from Walker tumour-bearing rats. Walker factor (WF) had no cytotoxic effects on myotube cells and morphological characteristics were not altered in the presence of WF and/or leucine. However, increased alkaline phosphatase activity was observed. At higher WE concentrations, chymotrypsin-like activity, cathepsin B activity and 20S proteasome gene expression increased. Treating myotubes with leucine before exposure to WF causes leads to a decrease in proteasome activity as well as the activity of chymotrypsin and cathepsin enzymes. Total protein synthesis decreased in WF-treated cells concomitantly as protein degradation increased. After leucine exposure, the observed effects of WF were minimal or even reverted in some cases. Taken together, these results suggest an important modulatory effect for leucine on the effects of WF in C2C12 myotube cells. (C) 2013 Elsevier Ltd. All rights reserved.