PDF(Pubmed)
Abstract：
Sodium butyrate (NaB) is one of the short-chain fatty acids and is notably produced in large amounts from dietary fiber in the gut. Recent evidence suggests that NaB induces cell proliferation and apoptosis. Skeletal muscle is rich in plenty of mitochondrial. However, it is unclear how NaB acts on host muscle cells and whether it is involved in mitochondria-related functions in myocytes. The present study aimed to investigate the role of NaB treatment on the proliferation, apoptosis, and mitophagy of bovine skeletal muscle satellite cells (BSCs). The results showed that NaB inhibited proliferation, promoted apoptosis of BSCs, and promoted mitophagy in a time- and dose-dependent manner in BSCs. In addition, 1 mM NaB increased the mitochondrial ROS level, decreased the mitochondrial membrane potential (MMP), increased the number of autophagic vesicles in mitochondria, and increased the mitochondrial DNA (mtDNA) and ATP level. The effects of the mTOR pathway on BSCs were investigated. The results showed that 1 mM NaB inhibited the mRNA and protein expression of mTOR and genes AKT1, FOXO1, and EIF4EBP1 in the mTOR signaling pathway. In contrast, the addition of PP242, an inhibitor of the mTOR signaling pathway also inhibited mRNA and protein expression levels of mTOR, AKT1, FOXO1, and EIF4EBP1 and promoted mitophagy and apoptosis, which were consistent with the effect of NaB treatment. NaB might promote mitophagy and apoptosis in BSCs by inhibiting the mTOR signaling pathway. Our results would expand the knowledge of sodium butyrate on bovine skeletal muscle cell state and mitochondrial function.
摘要：
丁酸钠(NaB)是短链脂肪酸中的一种,并且值得注意地从肠道中的膳食纤维大量产生。最近的证据表明NaB诱导细胞增殖和凋亡。骨骼肌富含大量线粒体。然而,目前尚不清楚NaB如何作用于宿主肌细胞，以及它是否参与肌细胞线粒体相关功能。本研究旨在探讨NaB处理对细胞增殖的影响,凋亡，和牛骨骼肌卫星细胞（BSC）的线粒体自噬。结果表明，NaB抑制细胞增殖，促进BSC的凋亡，并以时间和剂量依赖性方式促进BSC的线粒体自噬。此外,1mMNaB增加线粒体ROS水平，降低线粒体膜电位（MMP），增加线粒体中自噬囊泡的数量，并增加线粒体DNA（mtDNA）和ATP水平。研究了mTOR途径对BSC的影响。结果表明，1mMNaB抑制mTOR信号通路中mTOR及基因AKT1、FOXO1、EIF4EBP1的mRNA和蛋白表达。相比之下,添加PP242，mTOR信号通路的抑制剂也抑制mTOR的mRNA和蛋白表达水平，AKT1、FOXO1和EIF4EBP1促进线粒体自噬和凋亡，这与NaB治疗的效果一致。NaB可能通过抑制mTOR信号通路促进BSCs的线粒体自噬和凋亡。我们的结果将扩展丁酸钠对牛骨骼肌细胞状态和线粒体功能的认识。
