Fibronectin type III domain containing 5 expression in skeletal muscle in chronic heart failure-relevance of inflammatory cytokines.
Fibronectin type III domain containing 5 expression in skeletal muscle in chronic heart failure-relevance of inflammatory cytokines.
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DOI：
10.1002/jcsm.12006
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发表时间：
2015-03
影响因子：
8.9
通讯作者：
Adams, Volker
中科院分区：
文献类型：
--
作者：
Matsuo, Yae;Gleitsmann, Konstanze;Mangner, Norman;Werner, Sarah;Fischer, Tina;Bowen, T. Scott;Kricke, Angela;Matsumoto, Yasuharu;Kurabayashi, Masahiko;Schuler, Gerhard;Linke, Axel;Adams, Volker
慢性心力衰竭（CHF）通常与肌肉萎缩和炎症增加有关。Irisin是一种由纤连蛋白III型结构域5（FNDC 5）基因蛋白水解加工的肌细胞因子，被认为是过氧化物酶体增殖物激活受体γ共激活因子（PGC）-1α激活的，调节脂肪细胞的布朗宁并与肌肉质量相关。因此，我们研究了CHF中骨骼肌FNDC 5表达是否减少，以及这是否由炎性细胞因子和/或血管紧张素II（Ang-II）介导。在以下动物中分析骨骼肌FNDC 5 mRNA/蛋白和PGC-1α mRNA表达（任意单位）：（i）缺血性心肌病大鼠;（ii）注射肿瘤坏死因子-α（TNF-α）（24 h）的小鼠;（iii）输注Ang-II（4周）的小鼠;和（iv）暴露于重组细胞因子或Ang-II的C2 C12肌管。ELISA法检测循环TNF-α、Ang-II和Irisin。缺血性心肌病组FNDC 5蛋白（1.3 ± 0.2）和PGC-1α mRNA表达（8.2 ± 1.5）显著降低（P < 0.01），PGC-1α mRNA表达（4.7 ± 0.7）显著降低（P < 0.01）。体内TNF-α和Ang-II分别使FNDC 5蛋白表达降低28%和45%。用TNF-α、白细胞介素-1 β或TNF-α/白细胞介素-1 β孵育肌管，FNDC 5蛋白表达分别降低47%、37%或57%，而Ang-II无影响。PGC-1α与FNDC 5在所有条件下均呈线性相关。CHF时，动物循环TNF-α和Ang-II显著升高，而Irisin显著降低。循环TNF-α与Irisin呈明显负相关。缺血性心肌病中骨骼肌FNDC 5表达减少可能通过PGC-1α的下调受到炎性细胞因子和/或Ang-II的调节。这可能作为一种保护机制，通过减缓脂肪细胞的布朗宁和保持能量稳态或通过调节肌肉萎缩。
Chronic heart failure (CHF) is commonly associated with muscle atrophy and increased inflammation. Irisin, a myokine proteolytically processed by the fibronectin type III domain containing 5 (FNDC5) gene and suggested to be Peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α activated, modulates the browning of adipocytes and is related to muscle mass. Therefore, we investigated whether skeletal muscle FNDC5 expression in CHF was reduced and if this was mediated by inflammatory cytokines and/or angiotensin II (Ang-II). Skeletal muscle FNDC5 mRNA/protein and PGC-1α mRNA expression (arbitrary units) were analysed in: (i) rats with ischemic cardiomyopathy; (ii) mice injected with tumour necrosis factor-α (TNF-α) (24 h); (iii) mice infused with Ang-II (4 weeks); and (iv) C2C12 myotubes exposed to recombinant cytokines or Ang-II. Circulating TNF-α, Ang-II, and irisin was measured by ELISA. Ischemic cardiomyopathy reduced significantly FNDC5 protein (1.3 ± 0.2 vs. 0.5 ± 0.1) and PGC-1α mRNA expression (8.2 ± 1.5 vs. 4.7 ± 0.7). In vivo TNF-α and Ang-II reduced FNDC5 protein expression by 28% and 45%, respectively. Incubation of myotubes with TNF-α, interleukin-1ß, or TNF-α/interleukin-1ß reduced FNDC5 protein expression by 47%, 37%, or 57%, respectively, whereas Ang-II had no effect. PGC-1α was linearly correlated to FNDC5 in all conditions. In CHF, animals circulating TNF-α and Ang-II were significantly increased, whereas irisin was significantly reduced. A negative correlation between circulating TNF-α and irisin was evident. A reduced expression of skeletal muscle FNDC5 in ischemic cardiomyopathy is likely modulated by inflammatory cytokines and/or Ang-II via the down-regulation of PGC-1α. This may act as a protective mechanism either by slowing the browning of adipocytes and preserving energy homeostasis or by regulating muscle atrophy.
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氨基酸和胰岛素对人类肌肉中信号传导，泛素连接酶和蛋白质更新的作用之间的分离。
DOI：
10.1152/ajpendo.90411.2008
发表时间：
2008-09
期刊：
American journal of physiology. Endocrinology and metabolism
影响因子：
--
作者：
Greenhaff PL;Karagounis LG;Peirce N;Simpson EJ;Hazell M;Layfield R;Wackerhage H;Smith K;Atherton P;Selby A;Rennie MJ
通讯作者：
Rennie MJ
影响因子：
15.9
作者：
Acharyya, S;Ladner, KJ;Guttridge, DC
通讯作者：
Guttridge, DC
影响因子：
4.8
作者：
Lecker, SH;Jagoe, RT;Goldberg, AL
通讯作者：
Goldberg, AL
影响因子：
6.1
作者：
Felix, Klaus;Fakelman, Frederik;Werner, Jens
通讯作者：
Werner, Jens
DOI：
10.1097/spc.0b013e3283186be2
发表时间：
2008-12-01
影响因子：
2.1
作者：
Stephens, Nathan A;Skipworth, Richard J E;Fearon, Kenneth C H
通讯作者：
Fearon, Kenneth C H