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二氢杨梅素改变肌球蛋白重链表达 AMPK 信号通路在猪肌管。

Dihydromyricetin alters myosin heavy chain expression AMPK signaling pathway in porcine myotubes.

机构信息

Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan 611130, P. R. China.

College of Food Science, Sichuan Agricultural University, Yaan, Sichuan 625014, P. R. China.

出版信息

Food Funct. 2022 Oct 17;13(20):10525-10534. doi: 10.1039/d2fo02173k.

DOI:10.1039/d2fo02173k
PMID:36149397
Abstract

Dihydromyricetin (DHM) has attracted wide concern for its excellent biological function and pharmacological activities and was reported to have a positive effect on skeletal muscle insulin resistance, slow-twitch fibers expression and AMPK signaling. Thus, we took porcine myotubes derived from skeletal muscle satellite cells as the object to investigate the effects of DHM on myosin heavy chain (MyHC) expression and its mechanism in this study. Data showed that DHM up-regulated protein expression of MyHC I and down-regulated the protein expression of MyHC IIb, accompanied by an increase of mRNA level and a decrease of mRNA level. Besides, DHM increased the activities of malate dehydrogenase and succinic dehydrogenase and reduced lactate dehydrogenase activity. AMP-activated protein kinase (AMPK) was phosphorylated and mRNA level was increased by DHM. The AMPK signaling-related factors including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), sirtuin1 (Sirt1), nuclear respiratory factor 1 (NRF1), and phospho-calmodulin-dependent protein kinase kinase-β (p-CaMKKβ) were increased by DHM. Inhibition of the AMPK signaling by compound C and siRNA significantly attenuated the effects of DHM on expressions of MyHC I, MyHC IIb, PGC-1α and Sirt1. As a whole, DHM increased MyHC I expression and decreased MyHC IIb expression by the AMPK signaling.

摘要

二氢杨梅素(DHM)因其出色的生物学功能和药理活性而受到广泛关注,据报道,它对骨骼肌胰岛素抵抗、慢肌纤维表达和 AMPK 信号有积极作用。因此,本研究以骨骼肌卫星细胞衍生的猪肌管为对象,研究 DHM 对肌球蛋白重链(MyHC)表达的影响及其机制。结果表明,DHM 上调了 MyHC I 的蛋白表达,下调了 MyHC IIb 的蛋白表达,同时伴随着 mRNA 水平的增加和减少。此外,DHM 还增加了苹果酸脱氢酶和琥珀酸脱氢酶的活性,降低了乳酸脱氢酶的活性。DHM 还能磷酸化 AMP 激活的蛋白激酶(AMPK),增加其 mRNA 水平。DHM 还增加了过氧化物酶体增殖物激活受体γ共激活因子-1α(PGC-1α)、沉默信息调节因子 1(Sirt1)、核呼吸因子 1(NRF1)和磷酸钙调蛋白依赖性蛋白激酶激酶-β(p-CaMKKβ)等 AMPK 信号相关因子的表达。用化合物 C 和 siRNA 抑制 AMPK 信号后,DHM 对 MyHC I、MyHC IIb、PGC-1α 和 Sirt1 表达的影响明显减弱。总的来说,DHM 通过 AMPK 信号增加了 MyHC I 的表达,减少了 MyHC IIb 的表达。

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