Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway

  • Authors:
    • Moon Hee Lee
    • Min Ho Han
    • Dae-Sung Lee
    • Cheol Park
    • Su-Hyun Hong
    • Gi-Young Kim
    • Sang Hoon Hong
    • Kyoung Seob Song
    • Il-Whan Choi
    • Hee-Jae Cha
    • Yung Hyun Choi
  • View Affiliations

  • Published online on: December 23, 2016     https://doi.org/10.3892/ijmm.2016.2837
  • Pages: 399-406
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Abstract

In the present study, we investigated the cytoprotective efficacy of morin, a natural flavonoid, against oxidative stress and elucidated the underlying mechanisms in C2C12 myoblasts. Our results indicated that morin treatment prior to hydrogen peroxide (H2O2) exposure significantly increased cell viability and prevented the generation of reactive oxygen species. H2O2-induced comet-like DNA formation and γH2AX phosphorylation were also markedly suppressed by morin with a parallel inhibition of apoptosis in C2C12 myoblasts, suggesting that morin prevented H2O2-induced cellular DNA damage. Furthermore, morin markedly enhanced the expression of heme oxygenase-1 (HO-1) associated with the induction and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the inhibition of Kelch-like ECH-associated protein 1 (Keap1) expression. Notably, these events were eliminated by transient transfection with Nrf2‑specific small interfering RNA. Additional experiments demonstrated that the activation of the Nrf2/HO-1 pathway by morin was mediated by the extracellular signal‑regulated kinase (ERK) signaling cascade. This phenomenon was confirmed with suppressed Nrf2 phosphorylation and consequently diminished HO-1 expression in cells treated with a pharmacological inhibitor of ERK. Collectively, these results demonstrated that morin augments the cellular antioxidant defense capacity through the activation of Nrf2/HO‑1 signaling, which involves the activation of the ERK pathway, thereby protecting C2C12 myoblasts from H2O2-induced oxidative cytotoxicity.
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January 2017
Volume 39 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Lee, M.H., Han, M.H., Lee, D., Park, C., Hong, S., Kim, G. ... Choi, Y.H. (2017). Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway. International Journal of Molecular Medicine, 39, 399-406. https://doi.org/10.3892/ijmm.2016.2837
MLA
Lee, M. H., Han, M. H., Lee, D., Park, C., Hong, S., Kim, G., Hong, S. H., Song, K. S., Choi, I., Cha, H., Choi, Y. H."Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway". International Journal of Molecular Medicine 39.2 (2017): 399-406.
Chicago
Lee, M. H., Han, M. H., Lee, D., Park, C., Hong, S., Kim, G., Hong, S. H., Song, K. S., Choi, I., Cha, H., Choi, Y. H."Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway". International Journal of Molecular Medicine 39, no. 2 (2017): 399-406. https://doi.org/10.3892/ijmm.2016.2837