Tumor necrosis factor-α-induced apoptosis is associated with suppression of insulin-like growth factor binding protein-5 secretion in differentiating murine skeletal myoblasts

作     者：Meadows, KA Holly, JMP Stewart, CEH 

作者机构：Univ Bristol Bristol Royal Infirm Dept Surg Bristol BS2 8HW Avon England 

出 版 物：《JOURNAL OF CELLULAR PHYSIOLOGY》 (细胞生理学杂志)

年 卷 期：2000年第183卷第3期

页      面：330-337页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 071003[理学-生理学] 

主　　题：细胞凋亡/药物作用 细胞凋亡/生理学 细胞周期/药物作用 细胞周期/生理学 细胞系 肌酸激酶/分析 成纤维细胞生长因子2/药理学 胰岛素样生长因子结合蛋白质5/生物合成 胰岛素样生长因子结合蛋白质5/分泌 胰岛素样生长因子Ⅱ/生物合成 胰岛素样生长因子Ⅱ/分泌 肌 骨骼/细胞学 肌 骨骼/药物作用 肌 骨骼/生理学 重组蛋白质类/生物合成 重组蛋白质类/药理学 第二信使系统 鞘氨醇/类似物和衍生物 鞘氨醇/药理学 转染 肿瘤坏死因子α/药理学 动物 人类 小鼠 

摘      要：Wasting of muscle and fat during cachexia exceeds that explained by reduced food intake alone. This wasting may result from an imbalanced cytokine environment, which could lead to increased protein catabolism. Supporting this, tumor necrosis factor-alpha (TNF-alpha) is raised in several animal models of cachectic muscle wasting. Therefore, we assessed the effects of TNF-alpha and its second messenger, ceramide, on the proliferation, differentiation, and survival of murine C2 skeletal myoblasts. Because insulin-like growth factor binding protein-5 (IGFBP-5) and insulin-like growth factor-II (IGF-II) are potent regulators of myoblast proliferation and differentiation, we monitored the ability of exogenous TNF-alpha to manipulate this system. Fibroblast growth factor (FGF) ceramide, or TNF-alpha suppressed differentiation of C2 cells compared with controls. All treatments suppressed ICF-II production but only TNF-alpha blocked IGFBP-5 secretion. TNF-alpha increased apoptotic cell death, which otherwise remained basal (low serum differentiation medium (LSM), FGF) or low (ceramide). Suppression of both IGFBP-5 and IGF-II secretion may explain why of all triggers tested, only TNF-alpha not only blocked differentiation, but also promoted cell death. This suggests a fundamental role of IGFBP-5 for maintaining muscle survival. Supporting this hypothesis, no increase in apoptosis was seen in IGFBP-5 cDNA transfected C2 cells after TNF-alpha treatment. In summary, the IGF system is essential for maintaining skeletal muscle cell survival and differentiation, and its suppression by TNF-alpha is fundamental regarding muscle wasting, and may be associated in vivo with cancer cachexia. J. Cell. Physiol. 183:330-337, 2000. (C) 2000 Wiley-Liss, Inc.