title: 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.
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.
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Moon Hee
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Marine Biodiversity Institute of Korea, Seocheon 325-902, Republic of Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Han
authors.affiliation: Marine Biodiversity Institute of Korea, Seocheon 325-902, Republic of Korea.
authors.forename: Dae-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dongeui University, Busan 614-714, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Department of Physiology, Kosin University College of Medicine, Busan 602-072, Republic of Korea.
authors.forename: Kyoung Seob
authors.initials: KS
authors.lastname: Song
authors.affiliation: Department of Microbiology, College of Medicine, Inje University, Busan 608-737, Republic of Korea.
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.affiliation: Department of Parasitology and Genetics, Kosin University College of Medicine, Busan 602-072, Republic of Korea.
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004249:DNA Damage / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D047309:Flavones
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D005419:Flavonoids; D051547:Heme Oxygenase-1; D006861:Hydrogen Peroxide; D051267:NF-E2-Related Factor 2; D020011:Protective Agents; C008548:morin; D047309:Flavones