GROWTH OF THE HEART MUSCLE CELL

这项研究项目的目的是了解更多关于监管的 心肌细胞的增殖、分化和肥大 新生和成年大鼠原代培养体系及转基因 移植肿瘤心房肌细胞。我们特别感兴趣的是 与DNA合成重新启动有关的机制 在培养和AS中终末分化的成体细胞 TPA刺激和转基因小鼠DNA合成的重新启动 肌细胞。另一个主要目标是了解更多关于该结构如何 这些心肌细胞与它们的功能有关使用我们的初步 结果以TPA和环状AMP为模型。其基本原理是改变 结构，并寻找功能上的变化。具体目标是：1) 建立原癌基因表达的时间顺序， 新生儿肌肉特异性、细胞周期特异性和细胞骨架基因 心肌细胞被置于培养中，并受到环磷酸腺苷的影响。 2)在1)中建立基因表达的时间顺序 将成年心肌细胞置于培养期间， 去分化和再分化以及TPA的影响。3)至 检测这些基因在转基因心肌细胞中的表达 在细胞周期中的各个阶段。4)在时间上表征 在这些细胞培养系统中发生的超微结构变化 以及这些超微结构的变化如何与时间模式相关 1)中指定的基因的表达情况。4)比较……的表达 这些基因在这些不同的培养系统中相互关联并相互关联 在体内分化细胞以确定我们是否可以建立一种模式 这些基因的表达将表明它们可能如何在 控制心肌细胞的增殖和分化。 我们想要做的是建立一种因果关系 在结构和功能之间。如果我们能够理解 控制心肌细胞的分化和增殖， 那么就有可能设计出可以用来启动 或加速损伤后成人心肌的修复或再生 比如由心肌梗塞引起的。

The goal of this research project is to learn more about the regulation of cardiac muscle cell proliferation, differentiation and hypertrophy using both neonatal and adult rat primary culture systems and transgenic transplant tumor atrial myocytes. We are especially interested in the mechanisms involved with the reinitiation of DNA synthesis in the terminally differentiated adult cell when placed in culture and as stimulated by TPA and the reinitiation of DNA synthesis in transgenic mice myocytes. Another major objective is to learn more about how the structure of these heart muscle cells relates to their function using our preliminary results with TPA and cyclic AMP as models. The rationale being to alter structure and look for changes in function. The specific aims are: 1) To establish the temporal order of expression of protooncogenes, muscle-specific, cell cycle-specific, and cytoskeleton genes when neonatal cardiac muscle cells are placed in culture and as influenced by cyclic AMP. 2) To establish the temporal order of expression of the genes in 1) when adult cardiac muscle cells are placed in culture during the period of dedifferentiation and redifferentiation and as influenced by TPA. 3) To determine the expression of these genes in transgenic myocytes at various phases during the cell cycle. 4) To characterize temporally the ultrastructural changes which are occurring in these cell culture systems and how these changes in ultrastructure correlate with the temporal pattern of expression of the genes specified in 1). 4) To compare the expression of these genes in these different culture systems to each other and to the differentiating in vivo cell to determine if we can establish a pattern of expression of these genes which will indicate how they may function in the control of the proliferation and differentiation of the cardiac myocyte. What we would like to do is establish a cause and effect relationship between structure and function. If we can understand the mechanisms which control the differentiation and proliferation of the heart muscle cell, then it may be possible to design procedures which can be used to initiate or expedite repair or regeneration of the adult myocardium following injury such as that caused by a myocardial infraction.