Insulin-like growth factor-I blocks dexamethasone-induced protein degradation in cultured myotubes by inhibiting multiple proteolytic pathways: 2002 ABA paper.
Insulin-like growth factor-I blocks dexamethasone-induced protein degradation in cultured myotubes by inhibiting multiple proteolytic pathways: 2002 ABA paper.
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胰岛素样生长因子-I 通过抑制多种蛋白水解途径来阻断培养肌管中地塞米松诱导的蛋白质降解：2002 年 ABA 论文。
DOI：
10.1097/01.bcr.0000105100.44745.36
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Warden,GlennD
中科院分区：
文献类型：
--
作者：
Li,Bing-Guo;Hasselgren,Per-Olof;Fang,Cheng-Hui;Warden,GlennD
在以往的研究中，胰岛素样生长因子-i （IGF-I）抑制糖皮质激素诱导的肌肉蛋白分解，但IGF-I这种作用的细胞内机制尚不清楚。本研究的目的是验证igf - 1抑制地塞米松处理的培养L6肌管中多种蛋白水解途径的假设。在不含或存在0.1 μg/ml IGF-I的情况下，用1 μM地塞米松处理肌管6小时。蛋白质的降解是通过测量用3h -酪氨酸预标记的蛋白质释放的三氯乙酸溶性放射性来确定的。通过使用单个蛋白水解途径的抑制剂（分别为甲胺、β-内酯和E64）来评估溶酶体、蛋白酶体依赖和钙蛋白酶依赖的蛋白水解对IGF-I对蛋白质降解的抑制作用的贡献。此外，还测定了igf - 1对组织蛋白酶B、蛋白酶体和钙蛋白酶活性的影响。用地塞米松治疗L6肌管导致蛋白质降解增加约20%。地塞米松的这种作用被igf - 1完全阻断。当使用不同的蛋白酶抑制剂时，结果显示IGF-I分别抑制溶酶体、蛋白酶体依赖和钙蛋白酶依赖的蛋白水解，分别抑制70%、44%和41%。此外，igf - 1阻断地塞米松诱导的组织蛋白酶B、蛋白酶体和钙蛋白酶活性的升高。目前的研究结果表明，igf - 1通过阻断多种蛋白水解途径抑制糖皮质激素诱导的肌肉蛋白水解。
In previous studies, insulin-like growth factor-I (IGF-I) inhibited glucocorticoid-induced muscle protein breakdown, but the intracellular mechanisms of this effect of IGF-I are not well understood. The purpose of the present study was to test the hypothesis that IGF-I inhibits multiple proteolytic pathways in dexamethasone-treated cultured L6 myotubes. Myotubes were treated with 1 μM dexamethasone for 6 hours in the absence or presence of 0.1 μg/ml of IGF-I. Protein degradation was determined by measuring the release of trichloroacetic acid–soluble radioactivity from proteins prelabeled with3H-tyrosine. The contribution of lysosomal, proteasomal-dependent, and calpain-dependent proteolysis to the inhibitory effect of IGF-I on protein degradation was assessed by using inhibitors of the individual proteolytic pathways (methylamine, β-lactone, and E64, respectively). In addition, the influence of IGF-I on cathepsin B, proteasome, and calpain activities was determined. Treatment of L6 myotubes with dexamethasone resulted in an approximately 20% increase in protein degradation. This effect of dexamethasone was completely blocked by IGF-I. When the different protease inhibitors were used, results showed that IGF-I inhibited lysosomal, proteasomal-dependent, and calpain-dependent proteolysis by 70, 44, and 41%, respectively. Additionally, IGF-I blocked the dexamethasone-induced increase in cathepsin B, proteasome, and calpain activities. The present results suggest that IGF-I inhibits glucocorticoid-induced muscle proteolysis by blocking multiple proteolytic pathways.
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