STUDIES ON GROWTH SIGNALS DERIVED FROM PROTEIN NUTRITION

近年来分子生物学的研究表明，细胞的生长和增殖都需要生长信号及其信号转导。尽管幼龄动物的生长与营养状况有关，但营养与生长相关信号转导之间的相互作用尚未得到深入研究。我们研究的目的是确定蛋白质营养是否影响生长动物组织中细胞生长的信号转导，这取决于其营养质量。为此，我们研究了几个生长相关基因的表达和DNA合成在各种营养条件下生长大鼠的组织。本研究的主要结果如下：（1）生长期大鼠肝脏中c-myc和IGF-1 mRNA水平随饮食量或质的变化而呈交互性变化。与许多以前的工作相比，c-myc mRNA在营养不良的大鼠的肝脏中增加，其中生长被逮捕。(2)酪蛋白饲料喂养的大鼠保持在无蛋白饮食引起的c-myc mRNA的水平迅速下降，并诱导肝DNA合成。在此条件下，IGF-1 mRNA水平迅速增加。(3)玉米醇溶蛋白饮食，缺乏色氨酸和赖氨酸，没有改变c-myc和IGF-1的mRNA水平，也没有诱导DNA合成的肝脏，除非它补充色氨酸和赖氨酸。(4)当去除培养液中的氨基酸时，c-myc mRNA的表达量迅速增加，增加了18倍以上，说明c-myc的表达受营养环境的直接调控，提示营养不仅为幼年大鼠机体提供物质，而且影响细胞生长的信号传导。

Recent knowledge of molecular biology indicates that cell growth and proliferation are required growth signals and its signal transduction. Although growth of young animals is related to nutritional status, the interaction between nutrition and growth-related signal transduction has not been studied thoroughly. The aim of our study is to determine whether protein nutrition affects signal transduction for cell growth in the tissues of growing animals depending on its nutritional quality. For this purpose, we examined expression of several growth-related genes and DNA synthesis in tissues of growing rats under a variety of nutritional conditions. The results obtained under this project are ; (1) The levels of c-myc and insulin-like growth factor-1 (IGF-1) mRNA in the liver of growing rats varied in a reciprocal manner in response to changes in either quantity or quality of diet. In contrast to many previous works the c-myc mRNA increased in the liver of malnourished rats in which growth was arrested. (2) Feeding of casein diet to the rats maintained on protein-free diet caused rapid decrease in the level of c-myc mRNA and induced the DNA synthesis in the liver. The level of IGF-1 mRNA increased rapidly under this condition. (3) Zein diet, which lacks tryptophan and lysine, did not change the c-myc and the IGF-1 mRNA levels nor induced DNA synthesis in the liver unless it was supplemented with tryptophan and lysine. (4) The level of c-myc mRNA increased rapidly more than 18-fold when amino acids were removed from the medium indicating that the expression of c-myc was regulated directory by nutritional environment.In conclusion, lemphasize the possibility that nutrition not only supplies material for body components but also affects the signal transduction for cell growth in young growing rats.