Calycosin inhibited autophagy and oxidative stress in chronic kidney disease skeletal muscle atrophy by regulating AMPK/SKP2/CARM1 signalling pathway.
Calycosin inhibited autophagy and oxidative stress in chronic kidney disease skeletal muscle atrophy by regulating AMPK/SKP2/CARM1 signalling pathway.
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毛蕊异黄酮通过调节AMPK/SKP2/CARM1信号通路抑制慢性肾病骨骼肌萎缩中的自噬和氧化应激
DOI：
10.1111/jcmm.15514
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发表时间：
2020-10
影响因子：
5.3
通讯作者：
Wei LB
中科院分区：
文献类型：
--
作者：
Hu R;Wang MQ;Liu LY;You HY;Wu XH;Liu YY;Wang YJ;Lu L;Xiao W;Wei LB
骨骼肌萎缩是慢性肾脏病(CKD)常见而严重的并发症。氧化应激和自噬是肌肉萎缩的主要分子机制。毛冬青是黄芪的主要成分之一，具有抗炎、抗氧化、抗自噬等作用。我们研究了毛花菌素在体内和体外对骨骼肌萎缩的作用和机制。以5/6肾切除(5/6 NX)大鼠为CKD模型。测定体重和血清肌酐(Scr)、尿素氮(BUN)、白蛋白(Alb)水平。对CKD大鼠骨骼肌进行H&E染色、细胞凋亡、氧化应激生物标志物、自噬小体和LC3A/B水平的检测。毛花菌素治疗可改善CKD大鼠体重和肾功能，减轻肌肉萎缩(降低MuRF1和MAFbx水平)，提高超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)活性，降低丙二醛(MDA)水平。重要的是，花蕾菌素减少了自噬小体的形成，通过抑制AMPK和FOXO3a下调了LC3A/B和ATG7的表达，增加了Skp2的表达，导致CARM1、H3R17me2a的表达下降。在用肿瘤坏死因子-α和虫草素处理的C2C12细胞中也观察到了类似的结果。我们的研究结果表明，在慢性肾脏病引起的骨骼肌萎缩和肿瘤坏死因子-α诱导的C2C12肌管萎缩中，花蕾黄素抑制氧化应激和自噬，部分是通过调节AMPK/Skp2/CARM1信号通路。
Skeletal muscle atrophy is a common and serious complication of chronic kidney disease (CKD). Oxidative stress and autophagy are the primary molecular mechanisms involved in muscle atrophy. Calycosin, a major component of Radix astragali, exerts anti‐inflammatory, anti‐oxidative stress and anti‐autophagy effects. We investigated the effects and mechanisms of calycosin on skeletal muscle atrophy in vivo and in vitro. 5/6 nephrectomy (5/6 Nx) rats were used as a model of CKD. We evaluated bodyweight and levels of serum creatinine (SCr), blood urea nitrogen (BUN) and serum albumin (Alb). H&E staining, cell apoptosis, oxidative stress biomarkers, autophagosome and LC3A/B levels were performed and evaluated in skeletal muscle of CKD rat. Calycosin treatment improved bodyweight and renal function, alleviated muscle atrophy (decreased the levels of MuRF1 and MAFbx), increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH‐Px) activity and reduced malondialdehyde (MDA) levels in skeletal muscle of CKD rats. Importantly, calycosin reduced autophagosome formation, down‐regulated the expression of LC3A/B and ATG7 through inhibition of AMPK and FOXO3a, and increased SKP2, which resulted in decreased expression of CARM1, H3R17me2a. Similar results were observed in C2C12 cells treated with TNF‐α and calycosin. Our findings showed that calycosin inhibited oxidative stress and autophagy in CKD induced skeletal muscle atrophy and in TNF‐α‐induced C2C12 myotube atrophy, partially by regulating the AMPK/SKP2/CARM1 signalling pathway.
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影响因子：
11.1
作者：
He C;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
168.9
作者：
Matsushita, Kunihiro;van der Velde, Marije;Astor, Brad C.;Woodward, Mark;Levey, Andrew S.;de Jong, Paul E.;Coresh, Josef;Gansevoort, Ron T.
通讯作者：
Gansevoort, Ron T.
影响因子：
7.5
作者：
Ma, Ran;Yuan, Fang;Wang, Fulai
通讯作者：
Wang, Fulai
影响因子：
8.9
作者：
Aniort, Julien;Stella, Alexandre;Taillandier, Daniel
通讯作者：
Taillandier, Daniel
影响因子：
3.5
作者：
Auciello FR;Ross FA;Ikematsu N;Hardie DG
通讯作者：
Hardie DG