ACTIVITY INDUCED GROWTH OF SKELETAL MUSCLE

这项研究的目标是了解肌肉 活动以及结构和收缩需求会影响肌肉的大小 和功能。设计实验是为了探索坐标的性质 和细胞外结构适应性变化的分子基础 快、慢抽动的成分和功能或收缩成分 骨骼肌对超负荷诱导的肥大和去神经的反应- 松龙致小鼠在体肌萎缩及大鼠离体肌的机械应力 体外培养。拟议的研究将使用改进的传感新技术。 测量含量和速率的灵敏度和定量准确度 组织中两种主要胶原蛋白I型胶原的合成 和类型III。这些信息将与内容和 心肌细胞肌球蛋白重链和波形蛋白合成速率的研究 组织间充质细胞(成纤维细胞和血管内皮细胞 单元格)。我们将确定这些参数在中如何临时更改 在体模型中不同的肌肉纵向节段 以及改变的应激和神经支配，以及确定 通过控制组织中前胶原和肌球蛋白的合成速率 与测量的信使RNA变化的相关性 蛋白质。我们将测试不协调变化的假设 失神经肌肉的细胞外基质和心肌细胞蛋白含量 由于蛋白质和蛋白质周转率的不同反应 β-2肾上腺素能激动剂对血管周转率有不同的影响 组织中的胶原蛋白和肌球蛋白。被动的机制(S) 骨骼肌应激增加肌球蛋白和胶原的合成 将在体外系统中进行检查，最初的重点是 环AMP作为一个元件参与信号转导途径。这个 在这个项目中寻求的新信息是理解 生长和发育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前提条件 与了解候选人的行动性质和机制有关 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.