ACTIVITY INDUCED GROWTH OF SKELETAL MUSCLE

这项研究的目的是了解肌肉 活动以及由此产生的结构和收缩需求影响肌肉大小 和功能 实验旨在探索坐标性质 细胞外结构适应性变化的分子基础 快肌和慢肌的成分和功能性或收缩性成分 骨骼肌对超负荷诱导的肥大和去神经的反应- 在体内的离子诱导的萎缩和离体肌肉的机械应力， 体外 拟议的研究将使用新的技术，改善传感器， 测量的含量和速率的灵敏度和定量准确度 在组织中合成两种主要的胶原类型，I型胶原 和III型。 这些信息将与内容相关， 肌球蛋白重链和波形蛋白的合成率 组织的间充质细胞（成纤维细胞和血管内皮细胞 细胞）。 我们将确定这些参数是如何在时间上改变的， 体内模型中肌肉的不同纵向节段 改变的压力和神经支配，以及确定水平的 控制组织的前胶原和肌球蛋白的合成速率， 与特异性的信使RNA的测量变化的相关性 proteins. 我们将测试的假设，不协调的变化， 细胞外基质和肌细胞蛋白质含量在失神经肌肉， 由于蛋白质周转率的不同反应， β-2肾上腺素能激动剂不同程度地影响 组织中的胶原蛋白和肌球蛋白。 被动的机制 骨骼肌的应力增加肌球蛋白和胶原蛋白的合成 将在体外系统中进行检查，最初的重点是 作为转导途径中的元件的环AMP的参与。 的 在这个项目中寻求的新信息是了解 生长过程中细胞外基质变化的分子基础， 骨骼肌萎缩和确定靶反应的先决条件 与理解候选人的性质和作用机制有关 刺激组织的生长和重塑。

The goal of this research is to understand the mechanisms by which muscle activity and hence structural and contractile demands affect muscle size and function. Experiments are designed to explore the coordinate nature and molecular basis of the adaptive changes in extracellular architectural components and functional or contractile elements of fast- and slow-twitch skeletal muscles in response to overload-induced hypertrophy and denerva- tion-induced atrophy in vivo and mechanical stress of isolated muscles in vitro. The proposed research will use new techniques of improved sen- sitivity and quantitative accuracy to measure the content and rates of synthesis of the two major collagen types in the tissues, collagens type I and type III. This information will be correlated with the contents and rates of synthesis of myosin heavy chain in myocytes and vimentin in mesenchymal cells of the tissue (fibroblasts and blood vessel endothelial cells). We will determine how these parameters are altered temporally in different longitudinal segments of the muscles in the in vivo models of altered stress and innervation as well as determine the level of the control of rates of synthesis of procollagens and myosin of the tissue by correlations with measured changes in the messenger RNAs specific for the proteins. We will test the hypotheses that discoordinate changes in extracellular matrix and myocyte protein content in denervated muscles are due to differential responses in the turnover rates of the proteins and that beta-2 adrenergic agonists differentially effect the turnover rates of collagens versus myosin in the tissue. The mechanism(s) whereby passive stress of skeletal muscles increases the synthesis of myosin and collagen will be examined in an in vitro system with an initial focus on the participation of cyclic AMP as an element in the transducing pathway. The new information sought in this project is basic to understanding the molecular basis of changes in the extracellular matrix during growth and atrophy of skeletal muscle and prerequisite for defining target responses relevant to understanding the nature and mechanism of action of candidate stimuli for growth and remodeling of the tissue.