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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.
Gen Physiol Biophys 2017; 36(2):129-139GP

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+Show Affiliations

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.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28218609

Citation

Kang, Ji Sook, et al. "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." General Physiology and Biophysics, vol. 36, no. 2, 2017, pp. 129-139.
Kang JS, Kim GY, Kim BW, et al. 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. Gen Physiol Biophys. 2017;36(2):129-139.
Kang, J. S., Kim, G. Y., Kim, B. W., & Choi, Y. H. (2017). 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. General Physiology and Biophysics, 36(2), pp. 129-139. doi:10.4149/gpb_2016042.
Kang JS, et al. 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. Gen Physiol Biophys. 2017;36(2):129-139. PubMed PMID: 28218609.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Kang,Ji Sook, AU - Kim,Gi-Yiung, AU - Kim,Byung Woo, AU - Choi,Yung Hyun, Y1 - 2017/02/20/ PY - 2016/06/30/received PY - 2016/09/11/accepted PY - 2017/2/22/pubmed PY - 2017/6/20/medline PY - 2017/2/21/entrez SP - 129 EP - 139 JF - General physiology and biophysics JO - Gen. Physiol. Biophys. VL - 36 IS - 2 N2 - 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. SN - 0231-5882 UR - https://www.unboundmedicine.com/medline/citation/28218609/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_ L2 - http://www.aepress.sk/_downloads/dl.php?from=pubmed&journal=GPB&file=2017_02_129.pdf DB - PRIME DP - Unbound Medicine ER -