MOLECULAR MECHANISMS OF NEONATAL CARDIAC GROWTH

胎儿和新生动物心脏的生长涉及肌肉细胞 肥大和增生，并与组织增加相关 核糖核酸的含量。提高蛋白质的能力的程度 合成，如通过核糖体含量评估，或提高效率 现有的核糖体、信使核糖核酸以及起始和延伸因子 都是用在幼稚的心里没有研究过的。初步数据 在这个实验室中获得的结果表明，RNA含量增加是 影响总蛋白质速率较快的主要因素 在仔猪的心脏中合成。需要检验的假设是 细胞质核糖体的合成取决于速率之间的平衡 前rRNA合成和加工以及合成和加工速度之间的关系 核糖体蛋白的降解。合成纤维的严格测定 全心脏蛋白和核糖体蛋白以及rRNA的比率为 对于了解心脏生长的机制是必不可少的。收费率 心脏和心肌细胞中28S和18S RNA的合成 基于直接前体的特定活性，前rRNA和 将涉及用(~3H)尿苷或(甲基-~3H)蛋氨酸标记。费率 Pre-rRNA的合成将基于 放射性转化为Pre-rRNA，期间UTP的比活度 当Pre-rRNA标记上升时与稳态关系 组织中UTP的特异性活性与Pre-rRNA中的UMP之间的关系。 核糖体蛋白质的合成速度将基于特定的 苯丙氨酰-tRNA活性和放射性掺入速率 形成单个核糖体蛋白或核糖体核心蛋白。红心 从怀孕0.9天到出生10天的猪的发育 将会被比较。RNA和蛋白质合成的速度将在#年进行评估 左、右室游离壁和室间隔。左心室 游离壁生长速度是右室游离壁的3.5倍 长城在这些年龄段。心将会像兰登多夫和 具有模拟血浆含量的缓冲液的工作制剂 葡萄糖、乳酸、胰岛素和氨基酸。这些研究将允许 对rRNA合成和加工速度的严格估计 全心蛋白的合成和合成与掺入 R-蛋白转化为核糖体亚基。因此，早期事件发生在 未成熟心脏的快速生长将被发现，其机制 对正常的心肌生长会有更全面的了解。

Growth of the heart in fetal and neonatal animals involves muscle cell hypertrophy and hyperplasia and is associated with an increased tissue content of RNA. The extent to which elevated capacity for protein synthesis, as assessed by ribosome content, or improved efficiency with which the existing ribosomes, mRNA, and initiation and elongation factors are used has not been investigated in the immature heart. Preliminary data obtained in this laboratory suggest that increased RNA content is one of the major factors accounting for the faster rate of overall protein synthesis in the piglet heart. The hypothesis that is to be tested is that synthesis of cytoplasmic ribosomes depends upon the balance between rates of pre-rRNA synthesis and processing and between rates of synthesis and degradation of ribosomal proteins. A rigorous determination of synthetic rates for whole heart protein and ribosomal protein and for rRNA are essential for an understanding of mechanisms of cardiac growth. Rates of synthesis of 28S and 18S RNA in perfused hearts and heart muscle cells will be based on the specific activity of the immediate precursor, pre-rRNA and will involve labelling with (3H)uridine or (methyl-3H) methionine. Rates of synthesis of pre-rRNA will be based on the incorporation of radioactivity into pre-rRNA, the specific activity of UTP during the period when labelling of pre-rRNA is rising and the steady-state relationship between specific activities of UTP in the tissue and UMP in pre-rRNA. Rates of synthesis of ribosomal proteins will be based on the specific activity of phenylalanyl-tRNA and rates of incorporation of radioactivity into individual ribosomal proteins or ribosomal core proteins. The hearts of developing pigs from animals at 0.9 gestation to 10 days after birth will be compared. Rates of RNA and protein synthesis will be assessed in the right and left ventricular free walls and septum. The left ventricular free wall grows at a rate 3.5 times greater than the right ventricular free wall over these age ranges. Hearts will be perfused as Langendorff and working preparations with buffer that simulates the plasma content of glucose, lactate, insulin, and amino acids. These studies will allow for rigorous estimates of rates of synthesis and processing of rRNA, of synthesis of whole heart protein and of synthesis and incorporation of r-protein into ribosomal subunits. As a result, the early events during rapid growth of immature hearts will be identified and the mechanism of normal myocardial growth will be more completely understood.