Glycine administration attenuates skeletal muscle wasting in a mouse model of cancer cachexia
Glycine administration attenuates skeletal muscle wasting in a mouse model of cancer cachexia
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DOI：
10.1016/j.clnu.2013.06.013
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发表时间：
2014-06-01
影响因子：
6.3
通讯作者：
Koopman, Rene
中科院分区：
文献类型：
--
作者：
Ham, Daniel J.;Murphy, Kate T.;Koopman, Rene
背景和目的：甘氨酸是一种非必需氨基酸，通常被认为是生物中性的，但一些研究表明它可能是一种有效的抗炎药。由于炎症是癌症恶病质发展的核心，甘氨酸补充剂代表了一种简单、安全和有希望的治疗方法。我们验证了补充甘氨酸可以减少荷瘤小鼠骨骼肌炎症和保护肌肉质量的假设。方法：CD2F1小鼠按照Murphy等人的方案皮下注射PBS(对照组，n=12)或C26肿瘤细胞(n=32)，以诱导恶病质。访问数/每百万人：Reach for[Murphy KT，Chee A.功能和代谢损伤在描述C-26小鼠癌症恶病质模型中的重要性。DIS Models Mech 2012；5(4)：533-545.]结果：甘氨酸可减轻脂肪和肌肉质量的损失，抑制炎症标志物(F4/80，P=0.047.0 1和IL-6m RNA，P=0.0 1)和萎缩信号(MURF，P=0.047；阿托品-1，P=0.0 4；LC3B，P=0.0 6和P=0.0 6；BNIP3，P=0.10)，并倾向于减轻荷瘤小鼠的体重(P=0.07)、肌肉功能(P=0.06)和氧化应激(GSSG/GSH，P=0.06和DHE，P=0.07)。将甘氨酸与等氮剂量的丙氨酸或瓜氨酸的效果进行比较的初步研究表明，观察到的保护作用是针对甘氨酸的。结论：甘氨酸保护骨骼肌免受癌症引起的萎缩和功能丧失，减轻氧化和炎症负担，并减少癌症恶病质肌肉蛋白分解相关基因的表达。重要的是，这些影响是甘氨酸专一性的。(C)2013年爱思唯尔有限公司和欧洲临床营养与代谢学会。版权所有。
Background and aims: The non-essential amino acid, glycine, is often considered biologically neutral, but some studies indicate that it could be an effective anti-inflammatory agent. Since inflammation is central to the development of cancer cachexia, glycine supplementation represents a simple, safe and promising treatment. We tested the hypothesis that glycine supplementation reduces skeletal muscle inflammation and preserves muscle mass in tumor-bearing mice.Methods: To induce cachexia, CD2F1 mice received a subcutaneous injection of PBS (control, n = 12) or C26 tumor cells (n = 32) in accordance with the protocols developed by Murphy et al. [Murphy KT, Chee A, Trieu J, Naim T, Lynch GS. Importance of functional and metabolic impairments in the characterization of the C-26 murine model of cancer cachexia. Dis Models Mech 2012;5(4):533-545.]. Subcutaneous injections of glycine (n = 16) or PBS (n = 16) were administered daily for 21 days and at the conclusion of treatment, selected muscles, tumor and adipose tissue were collected and prepared for Real-Time RT-PCR or western blot analysis.Results: Glycine attenuated the loss of fat and muscle mass, blunted increases in markers of inflammation (F4/80, P = 0.01 & IL-6 mRNA, P = 0.01) and atrophic signaling (MuRF, P = 0.047; atrogin-1, P = 0.04; LC3B, P = 0.06 and; BNIP3, P = 0.10) and tended to attenuate the loss of body mass (P = 0.07), muscle function (P = 0.06), and oxidative stress (GSSG/GSH, P = 0.06 and DHE, P = 0.07) seen in tumor-bearing mice. Preliminary studies that compared the effect of glycine administration with isonitrogenous doses of alanine or citrulline showed that the observed protective effect was specific to glycine.Conclusions: Glycine protects skeletal muscle from cancer-induced wasting and loss of function, reduces the oxidative and inflammatory burden, and reduces the expression of genes associated with muscle protein breakdown in cancer cachexia. Importantly, these effects were glycine specific. (C) 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.