VITAMIN A IN GROWTH AND DEVELOPMENT

生长和发育中的维生素 A

• 批准号: 3311057
• 负责人: FRANK CHYTIL
• 金额: $ 19.76万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-05-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3311057
• 关键词: RNA; all trans retinol; analytical method; autoradiography; binding proteins; cell differentiation; cell nucleus; cytogenetics; developmental nutrition; electron microscopy; gene expression; genetic promoter element; genetic transcription; glucocorticoids; growth /development; histochemistry /cytochemistry; hormone regulation /control mechanism; immunochemistry; in situ hybridization; laboratory rat; liver; lung; mature animal; molecular pathology; newborn animals; nucleic acid hybridization; nucleoproteins; nutrition related tag; postnatal growth disorder; protein sequence; radioimmunoassay; radiotracer; retinoate; testis; tissue /cell culture; vitamin A deficiency; vitamin metabolism

The objective of the proposed nutritional and biochemical research is to continue to define molecular mechanism(s) of action of micronutrient vitamin A (retinol) and its metabolite retinoic acid in developing organs other than the eye. Retinol and retinoic acid interactions with the genome will be studied during perinatal development of lungs, liver, and testes. Changes which occur in the gene expression during retinol deficiency will be studied in the whole animal made retinol deficient by dietary restriction and shortly after refeeding with retinol or retinoic acid (refeeding model). In the analysis of interaction of this nutrient with the genome, two specific intracellular binding proteins for retinol (CRABP) and for retinoic acid (CRABP) will receive particular attention. Using the refeeding model, it will be explored whether and how the genes coding for these proteins are regulated by their respective ligands and by hormones. Furthermore, it will be studied how genes for these proteins are being regulated during perinatal development of various organs with special emphasis on the lung and testicular differentiation. The cells expressing genes for these binding proteins will be identified in pulmonary and testicular tissue. It will be attempted to clarify the tissue specific action of retinol and retinoic acid by studying proteins binding to the promoter regions of CRBP and CRABP genes. Finally, experiments are proposed to detect and characterize early genes activated by retinol and retinoic acid.

拟议的营养和生化研究的目的是 继续定义微量营养素作用的分子机制 发育器官中的维生素 A（视黄醇）及其代谢物视黄酸 除了眼睛之外。视黄醇和视黄酸与基因组的相互作用 将在肺、肝脏和睾丸的围产期发育期间进行研究。 视黄醇缺乏期间基因表达发生变化 在因饮食而缺乏视黄醇的整个动物中进行研究 限制以及重新喂食视黄醇或视黄酸后不久 （再喂食模型）。在分析该营养素与 基因组，两种特定的视黄醇细胞内结合蛋白（CRABP）和 视黄酸（CRABP）将受到特别关注。使用 再喂养模型中，将探讨基因是否以及如何编码 这些蛋白质受各自配体和激素的调节。 此外，还将研究这些蛋白质的基因是如何被改造的。 在围产期各个器官的发育过程中受到特殊调节 强调肺和睾丸的分化。表达的细胞 这些结合蛋白的基因将在肺和 睾丸组织。将尝试澄清组织的具体情况 通过研究与视黄醇和视黄酸结合的蛋白质的作用 CRBP 和 CRABP 基因的启动子区域。最后提出实验建议 检测和表征由视黄醇和视黄酸激活的早期基因 酸。