Gene regulation mediating fiber-type transformation in skeletal muscle cells is partly glucose- and ChREBP-dependent
Gene regulation mediating fiber-type transformation in skeletal muscle cells is partly glucose- and ChREBP-dependent
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DOI：
10.1016/j.bbamcr.2010.12.021
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发表时间：
2011-03-01
影响因子：
5.1
通讯作者：
Meissner, Joachim D.
中科院分区：
文献类型：
--
作者：
Hanke, Nina;Scheibe, Renate J.;Meissner, Joachim D.
骨骼肌细胞的氧化能力的适应可以在几种生理或病理条件下发生。我们研究了增加细胞外葡萄糖浓度对原代骨骼肌细胞和C2 C12肌细胞系中能量代谢标志物表达的影响。与5.55 mM相比，25 mM葡萄糖（高葡萄糖，HG）中肌管的生长导致甘油醛-3-磷酸脱氢酶（GAPDH）（糖酵解能量代谢的标志物）的表达和活性增加，而氧化标志物过氧化物酶体增殖物激活受体γ辅激活因子1 α和柠檬酸合酶减少。HG诱导代谢适应，如在慢到快的纤维转化期间所见。此外，HG增加快肌球蛋白重链（MHC）IId/x，但不改变慢MHC I/β表达。蛋白磷酸酶2A（PP 2A）介导HG对GAPDH和MHCIId/x的影响。碳水化合物反应元件结合蛋白（ChREBP），PP 2A下游的葡萄糖依赖性转录因子，部分介导葡萄糖对代谢标志物的影响。葡萄糖诱导的PP 2A活性的增加与p38促分裂原活化蛋白激酶活性的增加相关，这可能介导MHC 1d/x启动子活性的增加。肝脏X受体，另一种可能的葡萄糖效应介体，仅诱导不完全的代谢转变，主要是增加糖酵解标志物的表达。综上所述，HG诱导包含代谢酶的部分慢-快转化以及MHC 11 d/x的表达增加。这项工作证明了ChREBP在确定肌纤维代谢类型方面的功能作用，并强调了葡萄糖作为肌肉中信号分子的重要性。(c)2011 Elsevier B. V.保留所有权利。
Adaptations in the oxidative capacity of skeletal muscle cells can occur under several physiological or pathological conditions. We investigated the effect of increasing extracellular glucose concentration on the expression of markers of energy metabolism in primary skeletal muscle cells and the C2C12 muscle cell line. Growth of myotubes in 25 mM glucose (high glucose, HG) compared with 5.55 mM led to increases in the expression and activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a marker of glycolytic energy metabolism, while oxidative markers peroxisome proliferator-activated receptor gamma coactivator 1 alpha and citrate synthase decreased. HG induced metabolic adaptations as are seen during a slow-to-fast fiber transformation. Furthermore, HG increased fast myosin heavy chain (MHC) IId/x but did not change slow MHCI/beta expression. Protein phosphatase 2A (PP2A) was shown to mediate the effects of HG on GAPDH and MHCIId/x. Carbohydrate response element-binding protein (ChREBP), a glucose-dependent transcription factor downstream of PP2A, partially mediated the effects of glucose on metabolic markers. The glucose-induced increase in PP2A activity was associated with an increase in p38 mitogen-activated protein kinase activity, which presumably mediates the increase in MHCIld/x promoter activity. Liver X receptor, another possible mediator of glucose effects, induced only an incomplete metabolic shift, mainly increasing the expression of the glycolytic marker. Taken together, HG induces a partial slow-to-fast transformation comprising metabolic enzymes together with an increased expression of MHCIld/x. This work demonstrates a functional role for ChREBP in determining the metabolic type of muscle fibers and highlights the importance of glucose as a signaling molecule in muscle. (c) 2011 Elsevier B.V. All rights reserved.