title: Antioxidative effects of diallyl trisulfide on hydrogen peroxide-induced cytotoxicity through regulation of nuclear factor-E2-related factor-mediated thioredoxin reductase 1 expression in C2C12 skeletal muscle myoblast cells.
abstract: Diallyl trisulfide (DATS) is one of the major sulfur-containing compounds in garlic oil. In this study, we analyzed the effects of DATS against hydrogen peroxide (H2O2)-induced oxidative stress in C2C12 myoblasts. DATS preconditioning significantly attenuated H2O2-induced growth inhibition and DNA damage, as well as apoptosis by decreasing the generation of ROS. Treatment with DATS alone effectively upregulated the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and thioredoxin reductase 1 (TrxR1), which was associated with the increased phosphorylation of Nrf2. However, the protective effects of DATS against H2O2-induced growth reduction and ROS accumulation were significantly abolished by auranofin, an inhibitor of TrxR activity. Moreover, DATS-mediated phosphorylation of Nrf2 and induction of TrxR1 were markedly reduced by genetic silencing of Nrf2. DATS treatment also induced the phosphorylation extracellular signal-regulating kinase (ERK), and analysis using specific inhibitors of cellular signaling pathways demonstrated that only ERK activation was involved in Nrf2 phosphorylation and TrxR1 induction. In addition, the cytoprotective potentials were abrogated in C2C12 cells pretreated with an ERK specific inhibitor. The results demonstrate that DATS protects against oxidative stress-induced DNA damage and apoptosis in C2C12 cells in part through the activation of Nrf2-mediated TrxR1 induction via the ERK signaling pathway.
authors.affiliation: Anti-Aging Research Center and Blue-Bio Industry RIC, Dongeui University, 176 Eomgwangno Busanjin-gu, Busan 614-714, Republic of Korea. choiyh@deu.ac.kr.
authors.forename: Ji Sook
authors.initials: JS
authors.lastname: Kang
authors.forename: Gi-Yiung
authors.initials: GY
authors.lastname: Kim
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000498:Allyl Compounds / Q000008:administration & dosage*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000008:administration & dosage; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D032446:Myoblasts / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013440:Sulfides / Q000008:administration & dosage*; D054481:Thioredoxin Reductase 1 / Q000378:metabolism*
chemical_list: D000498:Allyl Compounds; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D013440:Sulfides; C042577:diallyl trisulfide; D006861:Hydrogen Peroxide; D054481:Thioredoxin Reductase 1; C516125:Txnrd1 protein, mouse