U.S.-Norway Cooperative Research: Compartmental Modeling ofthe Metabolism of Retinol and Retinol-Binding Protein

该奖项将使Michael H.Green博士能够与挪威奥斯陆大学的Kaare R.Norum博士、Rune Blomhoff博士和Trond Berg博士合作。他们将研究维生素A的新陈代谢，并将利用计算机辅助的、基于模型的隔室分析的独特方法，对以下数据进行分析：(1)维生素A充足的大鼠体内视黄醇和视黄醇结合蛋白(RBP)的周转；(2)维生素A缺乏的大鼠细胞内视黄醇的运输和分泌动力学；(3)受体介导的视黄醇/RBP在实质和星状大鼠肝细胞中的内吞动力学。他们的研究将有助于开发和量化生理相关的间隔模型，这些模型描述了全身和肝脏视黄醇和RBP代谢的动力学。他们将获得以下信息：(1)RBP和视黄醇在血浆、肝脏和肝外组织之间循环的性质和程度；(2)维生素A缺乏对肝脏调节途径的影响；(3)体外肝细胞中视黄醇和RBP的细胞内和亚细胞转运。拟议的实验是他们之前成功研究合作的延续和延伸。格林博士是维生素A分析方法、基于模型的隔室分析和全身维生素A新陈代谢方面的专家。挪威的研究人员在受体介导的内吞作用、肝细胞分离和培养以及维生素A代谢和方法方面特别熟练。

This award will enable Dr. Michael H. Green to collaborate with Drs. Kaare R. Norum, Rune Blomhoff, and Trond Berg, University of Oslo, Norway. They will study the metabolism of vitamin A and will apply the unique approach of computer-assisted, model-based compartmental analysis to data on (1) the in vivo turnover of retinol and retinol-binding protein (RBP) in vitamin A - sufficient rats, (2) the dynamics of intracellular transport and secretion of retinol in vitamin A - deficient rats, and (3) the kinetics of receptor-mediated endocytosis of retinol/RBP in parenchymal and stellate rat liver cells. Their studies will facilitate the development and quantification of physiologically relevant compartmental models which describe the dynamics of whole body and hepatic retinol and RBP metabolism. They will gain information on (1) the nature and extent of RBP vs. retinol recycling among plasma, liver, and extrahepatic tissues, (2) the hepatic regulatory pathways which are affected by vitamin A deficiency, and (3) the intracellular and subcellular transport of retinol and RBP in hepatic cells in vitro. The proposed experiments are a continuation and extension of their previous successful research collaboration. Dr. Green is an expert in analytical methods for vitamin A, model-based compartmental analysis, and whole body vitamin A metabolism. The Norwegian researchers are specially skilled in receptor-mediated endocytosis, liver cell separation and culture, and vitamin A metabolism and methods.