STRUCTURE AND FUNCTION OF TITIN IN CARDIAC MYOFIBRILS

这项研究的目的是确定titin在结构中的作用 以及心肌和骨骼肌肌原纤维的功能。这种蛋白质， 据报道，它占骨骼的10%，占骨骼的18% 心肌肌原纤维，其亚基大小超过100万道尔顿。 目前正在进行研究，以确定Titin在脑内的位置 使用单抗检测肌原纤维。两种荧光标记都打开 完整和部分提取的肌原纤维和免疫电子显微镜 我们会进行研究。将尝试确定是否 粗丝或细丝与分离的肌动蛋白或其他特定的 蛋白质(如结蛋白、α-肌动蛋白、肌球蛋白、星云蛋白等)可能 互动。将进行研究以确定Titin的关系 肌原纤维形成的表现。骨骼中Titin的准确含量 在Percoll梯度上纯化的心肌原纤维将 被分析。Titin特性随年龄的变化将在 正常和心肌萎缩的仓鼠心脏。Titin的弹性性质 与心脏高静息张力之间的明显关系 肌肉和高含量的肌动蛋白表明它可能在 心脏功能。Titin的变化和/或损害很可能涉及到 心脏病发作后或充血性心脏发生的改变 失败了。

The purpose of this study is to define the role ot titin in the structure and function of cardiac and skeletal muscle myofibrils. This protein, which has been reported to constitute as much as 10% of skeletal and 18% of cardiac myofibrils, has a subunit size in excess of 1,000,000 daltons. Studies are currently in progress to define the location of titin in the myofibril using monoclonal antibodies. Both fluorescence labeling on intact and partially extracted myofibrils and immunoelectron microscopic studies will be conducted. Attempts will be made to determine whether thick or thin filaments bind to isolated titin or whether other specific proteins (such as desmin, Alpha-actinin, myomesin, nebulin, etc.) may interact. Studies will be conducted to determine the relationship of titin appearance to myofibrillogenesis. The precise amount of titin in skeletal and cardiac myofibrils which have been purified on Percoll gradients will be analyzed. Changes in titin properties with age will be examined in normal and cardiomyopatihic hamster hearts. The elastic nature of titin and the apparent relationship between the high resting tension of cardiac muscle and the high titin content suggests it may play a key role in cardiac function. Changes and/or damage to titin may well be involved in the alterations occurring after a heart attack or in congestive heart failure.