DEVELOPMENTAL REGULATION OF HUMAN MUSCLE PROTEINS

点击翻译按钮获取中文摘要

Our long-range goal is to increase our understanding of the mechanisms underlying normal muscle development. From recent studies, it is clear that the developement of muscle in vivo is accompanied by a transition from embryonic-type to adult-type proteins. In the proposed studies, we will examine the requirements for expression of such developmentally regulated muscle isozymes in cultured human muscle cells. Specifically, the potential of human muscle satellite cells (muscle precursor cells) to express fetal and/or adult forms of glycogen phosphorylase and myosin will be examined in cultures derived from fetal and adult muscle. First, biochemical and immunological methods for detecting and characterizing the phosphorylase ans myosin isozymes typical of different stages of human muscle development will be perfected. Requirements for adult muscle isozyme expression will then be examined in cultured muscle satellite cells isolated from fetal and adult muscle tissues. To examine the intrinsic program of differentiation in these cells, developmental isozyme expression will be characterized in pure muscle cultures. To observe potential effects of neuronal modulation on isozyme expression, nerve-muscle co-cultures will be utilized. These experiments will establish conditions which permit expression of adult muscle proteins. They are also designed to determine whether the satellite cells of fetal and adult muscle differ in the type of muscle functions they express and whether the potential for mature isozyme expression increases with development. Since satellite cells play a critical role in both the development and regeneration of muscle in vivo, an understanding of satellite cell potential is of particular interest. Furthermore, delineation of normal satellite cell function may lead to an understanding of the etiology of human muscular dystrophies in which these cells may be defective. Finally, the ability to induce muscle phosphorylase in normal muscle cultures should facilitate analysis of the primary defect responsible for the failure in enzyme activity in vivo in McArdle's Disease (myophosphorylase deficiency).