Ⅱ型去乙酰化酶在有氧运动调节骨骼肌细胞葡萄糖代谢过程中的作用研究
发布时间：2018-08-06 12:32
【摘要】：研究目的:葡萄糖代谢异常是引发代谢相关疾病的重要因素之一。众所周知,规律的有氧运动是防治机体肥胖、胰岛素抵抗(IR)和2型糖尿病(T2DM)的有效手段。机体运动主要是通过骨骼肌收缩和舒张来完成,人体内约80%由胰岛素介导的葡萄糖转运和利用是由骨骼肌组织完成,因此,促进骨骼肌细胞葡萄糖代谢能够增强机体组织对胰岛素的敏感性,改善IR、预防T2DM的发生。Ⅱ型组蛋白去乙酰化酶(HDACs)作为转录抑制因子对组织细胞葡萄糖代谢起着重要的调节作用,Ⅱ型组蛋白去乙酰化酶中的HDAC4和HDAC5是运动敏感性的组蛋白去乙酰化酶。有氧运动作为预防和治疗肥胖、IR和多种代谢性疾病的有效手段,其作用机理是否与骨骼肌组织Ⅱ型HDACs的调控有关目前尚不完全明了。本研究以Ⅱ型HDACs调控组织细胞葡萄糖代谢为线索、以在体动物模型和离体细胞模型为对象,研究HDAC4和HDAC5在有氧运动改善骨骼肌细胞葡萄糖摄取及利用的作用机制。通过在体动物实验和离体细胞培养相结合的方式,研究有氧运动对C57BL/6小鼠骨骼肌细胞HDAC4和HDAC5调控葡萄糖转运体4(GLUT4)基因表达相互作用关系的影响;并在离体状态下探讨微小RNA-206(mi R-206)调节氧化型骨骼肌细胞HDAC4基因表达的具体机制,同时本研究还采用一磷酸腺苷活化蛋白激酶α2(AMPKα2)基因敲除小鼠,研究在AMPKα2缺失的情况下骨骼肌细胞HDAC4和HDAC5调控细胞葡萄糖代谢的变化,为进一步揭示HDAC4和HDAC5在骨骼肌细胞葡萄糖代谢中的作用机制提供理论依据。研究方法:1.动物模型的建立5周龄、雄性C57BL/6小鼠随机分为正常安静组(NC)和正常运动组(NE)。5周龄AMPKα2基因敲除小鼠共有三种基因型,即野生型(WT)、杂合子型(AMPKα2+/-)和纯合子型(AMPKα2-/-)。分别将各基因型小鼠随机分为安静对照组(C)和有氧运动组(E)。2.腺病毒的构建利用Gateway克隆技术构建HDAC4,HDAC5,MEF2A和AMPKα2过表达重组腺病毒质粒,采用Pac I内切酶线性化后转染293A细胞进行腺病毒包装。AMPKα2显性负突变腺病毒是通过Gateway克隆技术构建过表达质粒后进行点突变,再进行腺病毒载体的重组及包装。3.细胞培养及干预小鼠肌原细胞系C2C12经2%马血清培养诱导分化为肌管细胞。观察HDAC4,MEF2A和HDAC5过表达腺病毒以及HDAC4和HDAC5 si RNA干预肌管细胞对葡萄糖代谢的影响;检测AMPKα2过表达腺病毒及AMPKα2显性负突变腺病毒对肌管细胞HDAC4的影响;使用mi R-206 mimic和mi R-206 inhibitor转染肌管细胞,观察葡萄糖代谢的变化。4.生化指标检测采用Real-time PCR检测基因表达;采用Western Blot方法检测蛋白表达;使用2-脱氧葡萄糖荧光类似物(2-NBDG)检测C2C12肌管细胞葡萄糖摄取能力;采用免疫共沉淀(Co-IP)检测蛋白间的相互结合;采用免疫荧光检测蛋白表达及细胞内定位。研究结果:1.HDAC4/5在有氧运动改善骨骼肌糖代谢中的作用6周有氧运动可以显著增加小鼠骨骼肌组织GLUT4 m RNA和蛋白表达、HDAC4 Ser246位点磷酸化,同时促进HDAC4从细胞核转移至胞浆。通过离体细胞实验发现肌管细胞HDAC4表达的增加可抑制细胞GLUT4转录及其对葡萄糖摄取能力,当增加MEF2A的表达水平可逆转HDAC4的抑制作用。HDAC4 si RNA显著增加肌管细胞GLUT4基因转录水平,在此基础上给予HDAC5 si RNA,GLUT4基因转录水平被大幅度提高。与之相反,同时过表达HDAC4和HDAC5对于C2C12肌管细胞GLUT4的转录抑制效率显著高于单独过表达HDAC4或HDAC5。由此推测,骨骼肌细胞HDAC4与HDAC5可能在GLUT4的转录调控过程中发挥着协同作用。有氧运动显著降低氧化型肌纤维HDAC4和HDAC5蛋白表达,然而在酵解型肌纤维中却无显著变化。此外,有氧运动也显著降低骨骼肌细胞HDAC4和HDAC5的相互结合(图1.8)。由此提示,有氧运动对HDAC4和HDAC5蛋白表达调控具有肌纤维类型的特异性,对其下游靶基因的抑制作用可能与二者的相互结合有关。2.AMPKα2在有氧运动调控骨骼肌组织HDAC4/5中的作用离体状态下敲低AMPKα2可导致HDAC4 Ser246/632位点的磷酸化水平显著降低,促使HDAC4从细胞核转移至胞浆。提示骨骼肌细胞AMPKα2是HDAC4的上游激酶。单次有氧跑台运动可以激活野生型小鼠骨骼肌AMPK-HDAC4信号通路;然而有氧运动未能增加AMPKα2缺失小鼠骨骼肌HDAC4 Ser246/632磷酸化水平,提示运动对于骨骼肌组织HDAC4的激活依赖于AMPKα2。3.mi R-206介导HDAC4在有氧运动提高骨骼肌葡萄糖代谢中的作用机制6周的有氧运动显著增加氧化型肌纤维mi R-206的表达水平、抑制HDAC4蛋白表达、显著增加GLUT4 m RNA及蛋白表达。由此推测有氧运动可能通过mi R-206降低HDAC4的蛋白表达,进而增加骨骼肌细胞GLUT4的转录。离体研究发现,mi R-206水平的增高可显著降低HDAC4的蛋白表达、增加骨骼肌细胞GLUT4基因的转录、提高了骨骼肌细胞对葡萄糖的摄取。因此提示mi R-206可能通过抑制HDAC4促进骨骼肌细胞GLUT4的转录,进而增加了对葡萄糖的摄取能力。采用mi R-206 mimic和HDAC4 si RNA共转染肌管细胞,发现mi R-206和GLUT4的转录水平显著低于单独使用mi R-206 mimic干预的肌管细胞。随后检测发现,采用HDAC4 si RNA可显著降低C2C12肌管细胞mi R-206的表达水平,甚至与mi R-206 inhibitor干预后结果无显著差异。由此说明,HDAC4si RNA反馈性的抑制骨骼肌细胞mi R-206的表达。此外,以不同浓度梯度mi R-206 mimic孵育肌管细胞,GLUT4的基因表达随着浓度梯度增加而增加,之后转染肌管细胞过表达HDAC4腺病毒,GLUT4基因表达虽显著高于对照组,但显著低于单独使用mi R-206 mimic干预组,提示mi R-206通过HDAC4调控肌管细胞GLUT4的基因表达。研究结论:1.HDAC4通过MEF2A调控骨骼肌细胞GLUT4的基因转录,且在转录调控的过程中HDAC4/5可能发挥着协同作用。有氧运动对于HDAC4/5的影响具有肌纤维类型的特异性,唯有在氧化型肌纤维中的表达水平显著降低,可能是有氧运动促进骨骼肌有氧氧化,提高机体对糖脂代谢的重要机制。2.AMPK能够调控骨骼肌细胞HDAC4活性。单次有氧运动通过AMPKα2所依赖的方式激活骨骼肌细胞HDAC4。3.mi R-206 mimic显著抑制骨骼肌细胞HDAC4的蛋白表达,同时增加GLUT4转录、促进骨骼肌对葡萄糖的摄取。此外,有氧运动可能通过mi R-206调控氧化型肌纤维HDAC4的蛋白表达、促进机体的葡萄糖代谢。
[Abstract]:Objective: abnormal glucose metabolism is one of the important factors that cause metabolic related diseases. It is well known that regular aerobic exercise is an effective means to prevent body obesity, insulin resistance (IR) and type 2 diabetes (T2DM). Body exercise is accomplished mainly through skeletal muscle contraction and relaxation, and about 80% of the human body is mediated by insulin. Glucose transport and utilization are accomplished by skeletal muscle tissue. Therefore, promoting glucose metabolism in skeletal muscle cells can enhance the sensitivity of body tissue to insulin, improve IR and prevent the occurrence of T2DM. Type II histone deacetylase (HDACs) plays an important role in regulating glucose metabolism in tissue cells as a transcriptional inhibitor, type II egg HDAC4 and HDAC5 in white deacetylase are motor sensitive histone deacetylases. Aerobic exercise is an effective means to prevent and treat obesity, IR and multiple metabolic diseases. The mechanism of its action is not completely clear to the regulation of skeletal muscle type II HDACs. This study uses type II HDACs to regulate tissue cell Portuguese. Glucose metabolism was used as a clue to study the effect mechanism of HDAC4 and HDAC5 on improving glucose uptake and utilization of skeletal muscle cells by aerobic exercise in vivo animal model and isolated cell model. The HDAC4 and HDAC5 modulation of skeletal muscle cells in C57BL/6 mice was studied by combining in vivo and in vitro culture. The interaction relationship between the gene expression of glucose transporter 4 (GLUT4) was controlled, and the specific mechanism of the HDAC4 gene expression of the oxidized skeletal muscle cells regulated by tiny RNA-206 (MI R-206) was investigated in the isolated state, and the deletion of AMPK alpha 2 was also studied in this study by the gene knockout mice of adenosine activated protein kinase alpha 2 (AMPK alpha 2). The changes in skeletal muscle cells HDAC4 and HDAC5 regulate cell glucose metabolism and provide a theoretical basis for further revealing the mechanism of HDAC4 and HDAC5 in the glucose metabolism of skeletal muscle cells. The research methods: 1. animal models were established at 5 weeks of age, and male C57BL/6 mice were randomly divided into normal and quiet group (NC) and normal exercise group (NE).5 weeks AMP AMP There were three genotypes in K alpha 2 gene knockout mice, namely, wild type (WT), heterozygote type (AMPK alpha 2+/-) and homozygote type (AMPK alpha 2-/-). The mice were randomly divided into the quiet control group (C) and the aerobic exercise group (E).2. adenovirus construction using Gateway cloning technology to construct HDAC4, HDAC5, 2+/- and alpha 2 overexpressed the recombinant adenosine toxicity. After linearization of Pac I endonuclease, 293A cells were transfected into 293A cells to carry on the adenovirus packaging.AMPK alpha dominant negative mutation, and the overexpression plasmid was constructed by Gateway cloning technology to make the point mutation, then the recombinant adenovirus vector was reorganized and the.3. cell culture was packaged and the mouse myogenic cell line C2C12 was induced by 2% horse sera culture to induce differentiation. The effects of HDAC4, MEF2A and HDAC5 overexpressed adenoviruses and HDAC4 and HDAC5 Si RNA on glucose metabolism were observed, and the effects of AMPK a 2 overexpressed adenovirus and AMPK alpha 2 dominant negative mutant adenovirus on myotubular HDAC4 were detected. The changes of glucose metabolism.4. biochemical indexes were detected by Real-time PCR, Western Blot was used to detect protein expression, and 2- deoxyglucose fluorescence analogue (2-NBDG) was used to detect the glucose uptake ability of C2C12 myotube cells; immunofluorescence (Co-IP) was used to detect the interaction of protein, and the immunofluorescence was used to detect eggs. White expression and intracellular localization. Results: the effect of 1.HDAC4/5 on aerobic exercise improvement of skeletal muscle glucose metabolism 6 weeks of aerobic exercise can significantly increase the expression of GLUT4 m RNA and protein in skeletal muscle tissue of mice, phosphorylation of HDAC4 Ser246 site, and promote the transfer of HDAC4 from the nucleus to the cytoplasm. The myotube cell H is found through the cell experiment in vitro. The increase in expression of DAC4 inhibits the transcription of GLUT4 and its ability to absorb glucose, while increasing the expression level of MEF2A reverses the inhibition of HDAC4,.HDAC4 Si RNA significantly increases the transcriptional level of GLUT4 gene in myotube cells, on the basis of which HDAC5 Si RNA is given, and the transcriptional level of the GLUT4 gene is greatly increased. The transcriptional inhibition efficiency of HDAC4 and HDAC5 on C2C12 myotubular GLUT4 was significantly higher than that of HDAC4 or HDAC5. alone. The skeletal muscle cells HDAC4 and HDAC5 may play a synergistic role in the transcriptional regulation of GLUT4. Aerobic exercise significantly reduces the expression of HDAC4 and HDAC5 protein in the oxidized muscle fibers, however, in the glycolytic muscle fibers In addition, the aerobic exercise also significantly reduced the interaction of HDAC4 and HDAC5 in skeletal muscle cells (Figure 1.8). It suggests that the regulation of the expression of HDAC4 and HDAC5 proteins by aerobic exercise is specific to the type of muscle fiber, and the inhibition of the target gene of the downstream target may be associated with the interaction of the two persons with.2.AMPK alpha 2 in the aerobic exercise. The regulation of HDAC4/5 in skeletal muscle tissue in vitro knockout low AMPK alpha 2 can lead to a significant decrease in the phosphorylation level of the HDAC4 Ser246/632 site, prompting the transfer of HDAC4 from the nucleus to the cytoplasm. It suggests that the skeletal muscle cells AMPK alpha 2 is the upstream kinase of the HDAC4. The single aerobic table exercise can activate the AMPK-HDAC4 signal of the skeletal muscle of the wild type mice. However, aerobic exercise failed to increase the level of HDAC4 Ser246/632 phosphorylation in the skeletal muscle of AMPK alpha 2 deficient mice, suggesting that the activation of HDAC4 in skeletal muscle tissue depends on the mechanism of AMPK alpha 2.3.mi R-206 mediated HDAC4 in aerobic exercise to increase skeletal muscle glucose metabolism and the 6 week aerobic exercise significantly increases the mi R- of the oxidized muscle fibers. The expression level of 206 inhibits the expression of HDAC4 protein and significantly increases the expression of GLUT4 m RNA and protein. Therefore, it is suggested that aerobic exercise may reduce the expression of HDAC4 protein through mi R-206, and then increase the transcription of GLUT4 in skeletal muscle cells. In vitro studies have found that the increase of MI R-206 level can significantly reduce the HDAC4 protein expression and increase skeletal muscle cell GLUT4. Gene transcription increases the uptake of glucose in skeletal muscle cells. Therefore, MI R-206 may promote the transcription of GLUT4 in skeletal muscle cells by inhibiting HDAC4 and then increase the uptake of glucose. Mi R-206 mimic and HDAC4 Si RNA are used to co transfect myotube cells, and MI R-206 and transcriptional levels are found to be significantly lower than that of individual cells. It was found that the expression level of MI R-206 in C2C12 myotubular cells was significantly reduced by using HDAC4 Si RNA, and there was no significant difference between the C2C12 myotubular mi R-206 and the prognosis of MI R-206 inhibitor. 06 mimic incubated myotube cells, the gene expression of GLUT4 increased with the increase of concentration gradient and then transfected with myotube cells to overexpress HDAC4 adenovirus. The expression of GLUT4 gene was significantly higher than that of the control group, but it was significantly lower than the MI R-206 mimic intervention group, suggesting mi R-206 through HDAC4 to regulate the GLUT4 gene expression of myotube cells. 1.HDAC4 regulates the gene transcription of GLUT4 in skeletal muscle cells by MEF2A, and HDAC4/5 may play a synergistic role in the process of transcription regulation. The effect of aerobic exercise on HDAC4/5 has the specificity of the type of muscle fiber, only the expression level in the oxidized muscle fibers is significantly reduced, and it may be aerobic exercise to promote the aerobic oxidation of skeletal muscle. .2.AMPK, an important mechanism for the metabolism of glycolipid, can regulate the activity of HDAC4 in skeletal muscle cells. The activation of HDAC4.3.mi R-206 mimic in skeletal muscle cells by AMPK alpha 2 on single aerobic exercise significantly inhibits the protein expression of HDAC4 in skeletal muscle cells, and increases the GLUT4 conversion, and promotes the uptake of glucose in skeletal muscle. In addition, Aerobic exercise may regulate the protein expression of oxidized muscle fiber HDAC4 through mi R-206, and promote glucose metabolism in the body.
【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R87
本文编号：2167743
[Abstract]:Objective: abnormal glucose metabolism is one of the important factors that cause metabolic related diseases. It is well known that regular aerobic exercise is an effective means to prevent body obesity, insulin resistance (IR) and type 2 diabetes (T2DM). Body exercise is accomplished mainly through skeletal muscle contraction and relaxation, and about 80% of the human body is mediated by insulin. Glucose transport and utilization are accomplished by skeletal muscle tissue. Therefore, promoting glucose metabolism in skeletal muscle cells can enhance the sensitivity of body tissue to insulin, improve IR and prevent the occurrence of T2DM. Type II histone deacetylase (HDACs) plays an important role in regulating glucose metabolism in tissue cells as a transcriptional inhibitor, type II egg HDAC4 and HDAC5 in white deacetylase are motor sensitive histone deacetylases. Aerobic exercise is an effective means to prevent and treat obesity, IR and multiple metabolic diseases. The mechanism of its action is not completely clear to the regulation of skeletal muscle type II HDACs. This study uses type II HDACs to regulate tissue cell Portuguese. Glucose metabolism was used as a clue to study the effect mechanism of HDAC4 and HDAC5 on improving glucose uptake and utilization of skeletal muscle cells by aerobic exercise in vivo animal model and isolated cell model. The HDAC4 and HDAC5 modulation of skeletal muscle cells in C57BL/6 mice was studied by combining in vivo and in vitro culture. The interaction relationship between the gene expression of glucose transporter 4 (GLUT4) was controlled, and the specific mechanism of the HDAC4 gene expression of the oxidized skeletal muscle cells regulated by tiny RNA-206 (MI R-206) was investigated in the isolated state, and the deletion of AMPK alpha 2 was also studied in this study by the gene knockout mice of adenosine activated protein kinase alpha 2 (AMPK alpha 2). The changes in skeletal muscle cells HDAC4 and HDAC5 regulate cell glucose metabolism and provide a theoretical basis for further revealing the mechanism of HDAC4 and HDAC5 in the glucose metabolism of skeletal muscle cells. The research methods: 1. animal models were established at 5 weeks of age, and male C57BL/6 mice were randomly divided into normal and quiet group (NC) and normal exercise group (NE).5 weeks AMP AMP There were three genotypes in K alpha 2 gene knockout mice, namely, wild type (WT), heterozygote type (AMPK alpha 2+/-) and homozygote type (AMPK alpha 2-/-). The mice were randomly divided into the quiet control group (C) and the aerobic exercise group (E).2. adenovirus construction using Gateway cloning technology to construct HDAC4, HDAC5, 2+/- and alpha 2 overexpressed the recombinant adenosine toxicity. After linearization of Pac I endonuclease, 293A cells were transfected into 293A cells to carry on the adenovirus packaging.AMPK alpha dominant negative mutation, and the overexpression plasmid was constructed by Gateway cloning technology to make the point mutation, then the recombinant adenovirus vector was reorganized and the.3. cell culture was packaged and the mouse myogenic cell line C2C12 was induced by 2% horse sera culture to induce differentiation. The effects of HDAC4, MEF2A and HDAC5 overexpressed adenoviruses and HDAC4 and HDAC5 Si RNA on glucose metabolism were observed, and the effects of AMPK a 2 overexpressed adenovirus and AMPK alpha 2 dominant negative mutant adenovirus on myotubular HDAC4 were detected. The changes of glucose metabolism.4. biochemical indexes were detected by Real-time PCR, Western Blot was used to detect protein expression, and 2- deoxyglucose fluorescence analogue (2-NBDG) was used to detect the glucose uptake ability of C2C12 myotube cells; immunofluorescence (Co-IP) was used to detect the interaction of protein, and the immunofluorescence was used to detect eggs. White expression and intracellular localization. Results: the effect of 1.HDAC4/5 on aerobic exercise improvement of skeletal muscle glucose metabolism 6 weeks of aerobic exercise can significantly increase the expression of GLUT4 m RNA and protein in skeletal muscle tissue of mice, phosphorylation of HDAC4 Ser246 site, and promote the transfer of HDAC4 from the nucleus to the cytoplasm. The myotube cell H is found through the cell experiment in vitro. The increase in expression of DAC4 inhibits the transcription of GLUT4 and its ability to absorb glucose, while increasing the expression level of MEF2A reverses the inhibition of HDAC4,.HDAC4 Si RNA significantly increases the transcriptional level of GLUT4 gene in myotube cells, on the basis of which HDAC5 Si RNA is given, and the transcriptional level of the GLUT4 gene is greatly increased. The transcriptional inhibition efficiency of HDAC4 and HDAC5 on C2C12 myotubular GLUT4 was significantly higher than that of HDAC4 or HDAC5. alone. The skeletal muscle cells HDAC4 and HDAC5 may play a synergistic role in the transcriptional regulation of GLUT4. Aerobic exercise significantly reduces the expression of HDAC4 and HDAC5 protein in the oxidized muscle fibers, however, in the glycolytic muscle fibers In addition, the aerobic exercise also significantly reduced the interaction of HDAC4 and HDAC5 in skeletal muscle cells (Figure 1.8). It suggests that the regulation of the expression of HDAC4 and HDAC5 proteins by aerobic exercise is specific to the type of muscle fiber, and the inhibition of the target gene of the downstream target may be associated with the interaction of the two persons with.2.AMPK alpha 2 in the aerobic exercise. The regulation of HDAC4/5 in skeletal muscle tissue in vitro knockout low AMPK alpha 2 can lead to a significant decrease in the phosphorylation level of the HDAC4 Ser246/632 site, prompting the transfer of HDAC4 from the nucleus to the cytoplasm. It suggests that the skeletal muscle cells AMPK alpha 2 is the upstream kinase of the HDAC4. The single aerobic table exercise can activate the AMPK-HDAC4 signal of the skeletal muscle of the wild type mice. However, aerobic exercise failed to increase the level of HDAC4 Ser246/632 phosphorylation in the skeletal muscle of AMPK alpha 2 deficient mice, suggesting that the activation of HDAC4 in skeletal muscle tissue depends on the mechanism of AMPK alpha 2.3.mi R-206 mediated HDAC4 in aerobic exercise to increase skeletal muscle glucose metabolism and the 6 week aerobic exercise significantly increases the mi R- of the oxidized muscle fibers. The expression level of 206 inhibits the expression of HDAC4 protein and significantly increases the expression of GLUT4 m RNA and protein. Therefore, it is suggested that aerobic exercise may reduce the expression of HDAC4 protein through mi R-206, and then increase the transcription of GLUT4 in skeletal muscle cells. In vitro studies have found that the increase of MI R-206 level can significantly reduce the HDAC4 protein expression and increase skeletal muscle cell GLUT4. Gene transcription increases the uptake of glucose in skeletal muscle cells. Therefore, MI R-206 may promote the transcription of GLUT4 in skeletal muscle cells by inhibiting HDAC4 and then increase the uptake of glucose. Mi R-206 mimic and HDAC4 Si RNA are used to co transfect myotube cells, and MI R-206 and transcriptional levels are found to be significantly lower than that of individual cells. It was found that the expression level of MI R-206 in C2C12 myotubular cells was significantly reduced by using HDAC4 Si RNA, and there was no significant difference between the C2C12 myotubular mi R-206 and the prognosis of MI R-206 inhibitor. 06 mimic incubated myotube cells, the gene expression of GLUT4 increased with the increase of concentration gradient and then transfected with myotube cells to overexpress HDAC4 adenovirus. The expression of GLUT4 gene was significantly higher than that of the control group, but it was significantly lower than the MI R-206 mimic intervention group, suggesting mi R-206 through HDAC4 to regulate the GLUT4 gene expression of myotube cells. 1.HDAC4 regulates the gene transcription of GLUT4 in skeletal muscle cells by MEF2A, and HDAC4/5 may play a synergistic role in the process of transcription regulation. The effect of aerobic exercise on HDAC4/5 has the specificity of the type of muscle fiber, only the expression level in the oxidized muscle fibers is significantly reduced, and it may be aerobic exercise to promote the aerobic oxidation of skeletal muscle. .2.AMPK, an important mechanism for the metabolism of glycolipid, can regulate the activity of HDAC4 in skeletal muscle cells. The activation of HDAC4.3.mi R-206 mimic in skeletal muscle cells by AMPK alpha 2 on single aerobic exercise significantly inhibits the protein expression of HDAC4 in skeletal muscle cells, and increases the GLUT4 conversion, and promotes the uptake of glucose in skeletal muscle. In addition, Aerobic exercise may regulate the protein expression of oxidized muscle fiber HDAC4 through mi R-206, and promote glucose metabolism in the body.
【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R87
【参考文献】
相关期刊论文 前3条
1 Keith Richard Mitchelson;Wen-Yan Qin;;Roles of the canonical myomiRs mi R-1,-133 and-206 in cell development and disease[J];World Journal of Biological Chemistry;2015年03期
2 Jun-Yao Yang;Qian Wang;Wen Wang;Ling-Fang Zeng;;Histone deacetylases and cardiovascular cell lineage commitment[J];World Journal of Stem Cells;2015年05期
3 Lai Peng;Xiaobo Zhong;;Epigenetic regulation of drug metabolism and transport[J];Acta Pharmaceutica Sinica B;2015年02期
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