Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China.
Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China.
J Nutr Biochem. 2020 Mar;77:108297. doi: 10.1016/j.jnutbio.2019.108297. Epub 2019 Nov 27.
This study investigated the effects of resveratrol and miR-22-3p on muscle fiber type conversion in mouse C2C12 myotubes. Here we showed that resveratrol significantly increased the protein level of slow myosin heavy chain (MyHC) and the activities of succinic dehydrogenase and malate dehydrogenase, as well as markedly decreased the protein level of fast MyHC and the activity of lactate dehydrogenase. Immunofluorescence staining showed that resveratrol remarkably upregulated the number of slow MyHC-positive myotubes and downregulated the number of fast MyHC-positive myotubes, suggesting that resveratrol promoted muscle fiber type conversion from fast-twitch to slow-twitch in C2C12 myotubes. We also showed that miR-22-3p had an opposite function on muscle fiber type conversion and resveratrol was able to repress the expression of miR-22-3p. Furthermore, AMP-activated protein kinase (AMPK) inhibitor Compound C and miR-22-3p mimics could attenuate and eliminate muscle fiber type conversion from fast-twitch to slow-twitch cause by resveratrol, respectively. Together, we provided the first evidence that resveratrol promotes muscle fiber type conversion from fast-twitch to slow-twitch via miR-22-3p and AMPK/SIRT1/PGC-1α pathway in C2C12 myotubes.
本研究探讨了白藜芦醇和 miR-22-3p 对 C2C12 肌管中肌纤维类型转换的影响。结果表明，白藜芦醇显著增加了慢肌肌球蛋白重链（MyHC）蛋白水平和琥珀酸脱氢酶、苹果酸脱氢酶的活性，显著降低了快肌肌球蛋白重链蛋白水平和乳酸脱氢酶的活性。免疫荧光染色显示，白藜芦醇显著增加了慢肌 MyHC 阳性肌管的数量，降低了快肌 MyHC 阳性肌管的数量，表明白藜芦醇促进了 C2C12 肌管中从快肌向慢肌的肌纤维类型转换。我们还发现 miR-22-3p 对肌纤维类型转换具有相反的作用，白藜芦醇能够抑制 miR-22-3p 的表达。此外，AMP 激活的蛋白激酶（AMPK）抑制剂 Compound C 和 miR-22-3p 模拟物分别能够减弱和消除白藜芦醇引起的快肌向慢肌的肌纤维类型转换。综上所述，我们首次证明了白藜芦醇通过 miR-22-3p 和 AMPK/SIRT1/PGC-1α 通路促进 C2C12 肌管中从快肌向慢肌的肌纤维类型转换。
