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Int J Mol Med. 2017 Feb;39(2):399-406. doi: 10.3892/ijmm.2016.2837. Epub 2016 Dec 23.

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.

Author information

1
Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
2
Marine Biodiversity Institute of Korea, Seocheon 325-902, Republic of Korea.
3
Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University, Busan 614-714, Republic of Korea.
4
Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
5
Department of Internal Medicine, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
6
Department of Physiology, Kosin University College of Medicine, Busan 602-072, Republic of Korea.
7
Department of Microbiology, College of Medicine, Inje University, Busan 608-737, Republic of Korea.
8
Department of Parasitology and Genetics, Kosin University College of Medicine, Busan 602-072, Republic of Korea.

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.

PMID:
28035409
DOI:
10.3892/ijmm.2016.2837
[Indexed for MEDLINE]

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