Low molecular weight guluronate prevents TNF-α-induced oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells
Low molecular weight guluronate prevents TNF-α-induced oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells
复制标题
低分子量古洛糖醛酸可预防 TNF-α 诱导的 C2C12 骨骼肌细胞氧化损伤和线粒体功能障碍
DOI：
10.1039/c5fo00533g
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发表时间：
2015-01-01
期刊：
影响因子：
6.1
通讯作者：
Hao, Jie-jie
中科院分区：
文献类型：
--
作者：
Dun, Yun-lou;Zhou, Xiao-lin;Hao, Jie-jie
肌肉萎缩与多种慢性或炎性疾病有关。有证据表明，炎症细胞因子在肌肉炎症病理中起着至关重要的作用，这可能导致骨骼肌的氧化损伤和线粒体功能障碍。在我们的研究中，我们使用微波降解制备水溶性低分子量古洛糖醛酸（LMG）的3000 Da从墨角藻水泡，从加拿大，大西洋。我们通过HPLC、FTIR和NMR等方法研究了LMG的结构特征，并研究了LMG对肿瘤坏死因子α（TNF-α）诱导的C2 C12骨骼肌细胞氧化损伤和线粒体功能障碍的影响。结果表明，LMG能减轻TNF-α诱导的C2 C12细胞线粒体活性氧（ROS）的产生，提高抗氧化酶（GSH和SOD）的活性，提高线粒体膜电位（MMP），上调线粒体呼吸链蛋白的表达。补充LMG还增加了TNF-α诱导的C2 C12细胞中线粒体DNA拷贝数和线粒体生物发生相关基因。LMG可能通过核因子-κ B（NF-kappa B）信号通路发挥上述保护作用。这些表明LMG能够保护TNF-α诱导的C2 C12细胞免受氧化损伤和线粒体功能障碍。
Muscle wasting is associated with a variety of chronic or inflammatory disorders. Evidence suggests that inflammatory cytokines play a vital role in muscle inflammatory pathology and this may result in oxidative damage and mitochondrial dysfunction in skeletal muscle. In our study, we used microwave degradation to prepare a water-soluble low molecular weight guluronate (LMG) of 3000 Da from Fucus vesiculosus obtained from Canada, the Atlantic Ocean. We demonstrated the structural characteristics, using HPLC, FTIR and NMR of LMG and investigated its effects on oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells induced by tumor necrosis factor alpha (TNF-alpha), a cell inflammatory cytokine. The results indicated that LMG could alleviate mitochondrial reactive oxygen species (ROS) production, increase the activities of antioxidant enzymes (GSH and SOD), promote mitochondrial membrane potential (MMP) and upregulate the expression of mitochondrial respiratory chain protein in TNF-alpha-induced C2C12 cells. LMG supplement also increased the mitochondrial DNA copy number and mitochondrial biogenesis related genes in TNF-alpha-induced C2C12 cells. LMG may exert these protective effects through the nuclear factor kappa B (NF-kappa B) signaling pathway. These suggest that LMG is capable of protecting TNF-alpha-induced C2C12 cells against oxidative damage and mitochondrial dysfunction.