title: Low molecular weight guluronate prevents TNF-α-induced oxidative damage and mitochondrial dysfunction in C2C12 skeletal muscle cells.
abstract: 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-α), 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-α-induced C2C12 cells. LMG supplement also increased the mitochondrial DNA copy number and mitochondrial biogenesis related genes in TNF-α-induced C2C12 cells. LMG may exert these protective effects through the nuclear factor kappa B (NF-κB) signaling pathway. These suggest that LMG is capable of protecting TNF-α-induced C2C12 cells against oxidative damage and mitochondrial dysfunction.
authors.affiliation: Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. 2009haojie@ouc.edu.cn.
authors.forename: Yun-lou
authors.initials: YL
authors.lastname: Dun
authors.forename: Xiao-lin
authors.initials: XL
authors.lastname: Zhou
authors.forename: Hua-shi
authors.initials: HS
authors.lastname: Guan
authors.forename: Guang-li
authors.initials: GL
authors.lastname: Yu
authors.forename: Chun-xia
authors.initials: CX
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Hu
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.forename: Xiao-lei
authors.initials: XL
authors.lastname: Cheng
authors.forename: Xiao-xi
authors.initials: XX
authors.lastname: He
authors.forename: Jie-jie
authors.initials: JJ
authors.lastname: Hao
mesh_terms: D000818:Animals; D002100:Cachexia / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D002460:Cell Line; D044645:Fucus / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008970:Molecular Weight; D032342:Muscle Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012624:Seaweed / Q000737:chemistry; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D006603:Hexuronic Acids; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C007896:guluronic acid; D013482:Superoxide Dismutase; D005978:Glutathione