Ginsenoside compound K ameliorates palmitate-induced atrophy in C2C12 myotubes via promyogenic effects and AMPK/autophagy-mediated suppression of endoplasmic reticulum stress.
Ginsenoside compound K ameliorates palmitate-induced atrophy in C2C12 myotubes via promyogenic effects and AMPK/autophagy-mediated suppression of endoplasmic reticulum stress.
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DOI：
10.1016/j.jgr.2021.09.002
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发表时间：
2022-05
影响因子：
6.3
通讯作者：
Tae Woo Jung
中科院分区：
文献类型：
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作者：
Tae Jin Kim;Do Hyeon Pyun;Myeong Jun Kim;Ji Hoon Jeong;El-Aty, A. M. A.;Tae Woo Jung
化合物K(CK)是原人参二醇(PPD)类人参皂苷类化合物，具有多种药理作用。在此，我们研究了CK在高脂条件下对肌肉萎缩的影响以及它的促肌生成作用。此外，CK对骨骼肌影响的分子途径已经被证明是合理的。C2C12肌管分别用棕榈酸酯和CK处理。用CK诱导C2C12成肌细胞分化4~5d。在体内实验中，CK被给予高脂饮食喂养的小鼠8周。Western blotting分析蛋白质表达水平。通过小干扰(Si)RNA转染法抑制靶蛋白表达。组织学检查采用Jenner-Giemsa和H&E染色技术。CK处理可降低高脂饮食小鼠经棕榈酸酯处理的C2C12肌管和骨骼肌中eIF2α磷酸化和CHOP表达等ER应激标志物，并损害肌管的形成。在体外和体内实验中，CK处理增加了骨骼肌细胞中的AMPK和自噬标记。AMPK siRNA或自噬抑制剂3-MA可阻断CK对C2C12肌管的影响。CK处理增强了p38和Akt的磷酸化，导致C2C12的肌原生成增强。然而，AMPK siRNA可阻断CK对C2C12成肌细胞的作用。这些发现表明，CK通过AMPK/自噬介导的减轻内质网应激和诱导成肌细胞分化来阻止脂质诱导的骨骼肌细胞凋亡。因此，我们可以建议使用CK作为一种潜在的治疗方法来治疗与肥胖相关的肌肉萎缩情况。
Compound K (CK) is among the protopanaxadiol (PPD)-type ginsenoside group, which produces multiple pharmacological effects. Herein, we examined the effects of CK on muscle atrophy under hyperlipidemic conditions along with its pro-myogenic effects. Further, the molecular pathways underlying the effects of CK on skeletal muscle have been justified. C2C12 myotubes were treated with palmitate and CK. C2C12 myoblasts were differentiated using CK for 4–5 days. For the in vivo experiments, CK was administered to mice fed on a high-fat diet for 8 weeks. The protein expression levels were analyzed using western blotting analysis. Target protein suppression was performed using small interfering (si) RNA transfection. Histological examination was performed using Jenner-Giemsa and H&E staining techniques. CK treatment attenuated ER stress markers, such as eIF2α phosphorylation and CHOP expression and impaired myotube formation in palmitate-treated C2C12 myotubes and skeletal muscle of mice fed on HFD. CK treatment augmented AMPK along with autophagy markers in skeletal muscle cells in vitro and in vivo experiments. AMPK siRNA or 3-MA, an autophagy inhibitor, abrogated the impacts of CK in C2C12 myotubes. CK treatment augmented p38 and Akt phosphorylation, leading to an enhancement of C2C12 myogenesis. However, AMPK siRNA abolished the effects of CK in C2C12 myoblasts. These findings denote that CK prevents lipid-induced skeletal muscle apoptosis via AMPK/autophagy-mediated attenuation of ER stress and induction of myoblast differentiation. Therefore, we may suggest the use of CK as a potential therapeutic approach for treating muscle-wasting conditions associated with obesity.