Morin attenuates dexamethasone-mediated oxidative stress and atrophy in mouse C2C12 skeletal myotubes

Anayt Ulla, Takayuki Uchida, Yukari Miki, Kosuke Sugiura, Atsushi Higashitani, Takeshi Kobayashi, Ayako Ohno, Reiko Nakao, Katsuya Hirasaka, Iori Sakakibara, Takeshi Nikawa

Research output: Contribution to journalArticlepeer-review

Abstract

Glucocorticoids are the drugs most commonly used to manage inflammatory diseases. However, they are prone to inducing muscle atrophy by increasing muscle proteolysis and decreasing protein synthesis. Various studies have demonstrated that antioxidants can mitigate glucocorticoid-induced skeletal muscle atrophy. Here, we investigated the effect of a potent antioxidative natural flavonoid, morin, on the muscle atrophy and oxidative stress induced by dexamethasone (Dex) using mouse C2C12 skeletal myotubes. Dex (10 μM) enhanced the production of reactive oxygen species (ROS) in C2C12 myotubes via glucocorticoid receptor. Moreover, Dex administration reduced the diameter and expression levels of the myosin heavy chain protein in C2C12 myotubes, together with the upregulation of muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box protein 1/atrogin-1, muscle ring finger protein-1, and casitas B-lineage lymphoma proto-oncogene-b. Dex also significantly decreased phosphorylated Foxo3a and increased total Foxo3a expression. Interestingly, Dex-induced ROS accumulation and Foxo3a expression were inhibited by morin (10 μM) pretreatment. Morin also prevented the Dex-induced reduction of myotube thickness, together with muscle protein degradation and suppression of the upregulation of atrophy-associated ubiquitin ligases. In conclusion, our results suggest that morin effectively prevents glucocorticoid-induced muscle atrophy by reducing oxidative stress.

Original languageEnglish
Article number108873
JournalArchives of Biochemistry and Biophysics
Volume704
DOIs
Publication statusPublished - 2021 Jun 15

Keywords

  • Morin
  • Mouse C2C12 skeletal myotubes
  • Muscle atrophy
  • Reactive oxygen species
  • Ubiquitin ligases

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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