MOLECULAR MECHANISMS OF NEONATAL CARDIAC GROWTH

胎儿和新生动物心脏的生长涉及肌细胞 肥大和增生，并与增加的组织 RNA的含量。 蛋白质摄入量的增加 合成，如通过核糖体含量评估的，或用 现有的核糖体、mRNA、起始和延伸因子 尚未在未成熟心脏中进行研究。 初步数据 在这个实验室中获得的结果表明，RNA含量的增加是 占总蛋白质速率较快的主要因素 在猪仔心脏中合成。 有待检验的假设是， 细胞质核糖体的合成取决于 前rRNA合成和加工的速率以及合成和加工的速率之间的关系。 核糖体蛋白降解。 严格测定合成的 全心脏蛋白和核糖体蛋白以及rRNA的比率为 这对于理解心脏生长的机制至关重要。 率 灌注心脏和心肌细胞中28 S和18 S RNA的合成将 基于直接前体、pre-rRNA和 将涉及用（3 H）尿苷或（甲基-3H）甲硫氨酸标记。 率 前体rRNA的合成将基于掺入 放射性转化为前rRNA，在此期间UTP的比活性 当前体rRNA的标记增加时， 组织中UTP的特异性活性与前体rRNA中UMP的特异性活性之间的关系。 核糖体蛋白的合成速率将基于特定的 苯丙氨酰-tRNA的活性和放射性掺入率 单个的核糖体蛋白或核糖体核心蛋白。 心中 从妊娠0.9天到出生后10天的动物中， 将被比较。 RNA和蛋白质合成的速率将在 右心室和左心室游离壁和间隔。 左心室 游离壁的生长速度是右心室游离壁的3.5倍 在这些年龄段的墙上。 心脏将被灌注为Langendorff和 用模拟血浆含量的缓冲液制备 葡萄糖、乳酸盐、胰岛素和氨基酸。 这些研究将使 严格估计rRNA的合成和加工速率， 全心脏蛋白的合成以及 R蛋白转化为核糖体亚基。 因此，早期的事件 未成熟心脏的快速生长将被确定， 将更全面地了解正常的心肌生长。

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.