研究动态
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癌症恶病质中抗生素诱导的微生物干扰后骨骼肌蛋白质组的修饰。

Skeletal Muscle Proteome Modifications following Antibiotic-Induced Microbial Disturbances in Cancer Cachexia.

发表日期:2024 Jul 05
作者: Mathilde Simonson, Gwendal Cueff, Morgane M Thibaut, Christophe Giraudet, Jérôme Salles, Christophe Chambon, Yves Boirie, Laure B Bindels, Marine Gueugneau, Christelle Guillet
来源: JOURNAL OF PROTEOME RESEARCH

摘要:

癌症恶病质是一种非自愿的体重减轻,主要是骨骼肌的体重减轻。先前的研究支持微生物群-肌肉串扰的存在,因此该研究的目的是评估抗生素引起的微生物群改变对骨骼肌蛋白表达的影响。在接受或不接受抗生素治疗的对照 (CT) 或 C26 恶病质小鼠 (C26) 中研究骨骼肌蛋白质组变化(CT-ATB 或 C26-ATB,每组 n = 8)。将肌肉蛋白提取物分为肌浆和肌原纤维部分,然后进行无标记液相色谱分离、质谱分析、Mascot蛋白鉴定和METASCAPE平台数据分析。在C26小鼠中,atrogen mafbx表达比CT小鼠高353%,比C26-ATB小鼠高42.3%。没有观察到对肌肉蛋白质合成的影响。蛋白质组学分析揭示了抗生素对恶病质之外的骨骼肌蛋白质组有强烈影响,其适应性过程涉及蛋白质折叠、生长、能量代谢和肌肉收缩。在 C26-ATB 小鼠中,在 CT-ATB 小鼠中观察到的蛋白质组适应性减弱。差异表达的蛋白质参与其他过程,如葡萄糖代谢、氧化应激反应和蛋白水解。这项研究证实了微生物群-肌肉轴的存在,抗生素后的肌肉反应根据是否存在恶病质而变化。
Cancer cachexia is an involuntary loss of body weight, mostly of skeletal muscle. Previous research favors the existence of a microbiota-muscle crosstalk, so the aim of the study was to evaluate the impact of microbiota alterations induced by antibiotics on skeletal muscle proteins expression. Skeletal muscle proteome changes were investigated in control (CT) or C26 cachectic mice (C26) with or without antibiotic treatment (CT-ATB or C26-ATB, n = 8 per group). Muscle protein extracts were divided into a sarcoplasmic and myofibrillar fraction and then underwent label-free liquid chromatography separation, mass spectrometry analysis, Mascot protein identification, and METASCAPE platform data analysis. In C26 mice, the atrogen mafbx expression was 353% higher than CT mice and 42.3% higher than C26-ATB mice. No effect on the muscle protein synthesis was observed. Proteomic analyses revealed a strong effect of antibiotics on skeletal muscle proteome outside of cachexia, with adaptative processes involved in protein folding, growth, energy metabolism, and muscle contraction. In C26-ATB mice, proteome adaptations observed in CT-ATB mice were blunted. Differentially expressed proteins were involved in other processes like glucose metabolism, oxidative stress response, and proteolysis. This study confirms the existence of a microbiota-muscle axis, with a muscle response after antibiotics that varies depending on whether cachexia is present.