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首页> 外文期刊>Nutrition >Comparison of the anticatabolic effects of leucine and Ca-β-hydroxy-β-methylbutyrate in experimental models of cancer cachexia
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Comparison of the anticatabolic effects of leucine and Ca-β-hydroxy-β-methylbutyrate in experimental models of cancer cachexia

机译：亮氨酸和Ca-β-羟基-β-甲基丁酯在癌症癌症癌症实验模型中的抗真实效应的比较

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Objective: Loss of skeletal muscle is the most debilitating feature of cancer cachexia, and there are few treatments available. The aim of this study was to compare the anticatabolic efficacy of L-leucine and the leucine metabolite β-hydroxy-β-methylbutyrate (Ca-HMB) on muscle protein metabolism, both invitro and invivo. Methods: Studies were conducted in mice bearing the cachexia-inducing murine adenocarcinoma 16 tumor, and in murine C2 C12 myotubes exposed to proteolysis-inducing factor, lipopolysaccharide, and angiotensin II. Results: Both leucine and HMB were found to attenuate the increase in protein degradation and the decrease in protein synthesis in murine myotubes induced by proteolysis-inducing factor, lipopolysaccharide, and angiotensin II. However, HMB was more potent than leucine, because HMB at 50 μM produced essentially the same effect as leucine at 1 mM. Both leucine and HMB reduced the activity of the ubiquitin-proteasome pathway as measured by the functional (chymotrypsin-like) enzyme activity of the proteasome in muscle lysates, as well as Western blot quantitation of protein levels of the structural/enzymatic proteasome subunits (20 S and 19 S) and the ubiquitin ligases (MuRF1 and MAFbx). Invivo studies in mice bearing the murine adenocarcinoma 16 tumor showed a low dose of Ca-HMB (0.25 g/kg) tobe 60% more effective than leucine (1 g/kg) in attenuating loss of body weight over a 4-d period. Conclusion: These results favor the clinical feasibility of using Ca-HMB over high doses of leucine for the treatment of cancer cachexia.
机译：目的：骨骼肌的丧失是癌症恶病症最令人衰弱的特征，并且有很少的治疗方法。本研究的目的是将L-亮氨酸和亮氨酸代谢物β-羟基-β-甲基丁酯（CA-HMB）对肌肉蛋白质代谢（invirogro和Invivo）的抗粘性效果进行比较。方法：在载体诱导鼠腺癌16肿瘤中的小鼠中进行研究，并在鼠C2 C12肌管中暴露于蛋白水解诱导因子，脂多糖和血管紧张素II。结果：亮氨酸和HMB均发现蛋白质诱导因子，脂多糖和血管紧张素II诱导的鼠霉素中蛋白质降解的增加和蛋白质合成的增加。然而，HMB比亮氨酸更有效，因为50μm的HMB产生的效果与1mm的亮氨酸相同。亮氨酸和HMB均可通过肌肉裂解物中蛋白酶体的功能（Chymotrypsin）酶活性，以及​​结构/酶蛋白酶体亚基的蛋白质水平的蛋白质水平的蛋白质水平（20 S和19 s）和泛素连接酶（Murf1和Mafbx）。载有鼠腺癌16颗粒的监管研究表明，低剂量的Ca-HMB（0.25g / kg），比亮氨酸（1g / kg）更有效，在4-D期间衰减体重损失。结论：这些结果有利于在高剂量亮氨酸上使用Ca-HMB治疗癌症恶病症的临床可行性。

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