Multidrug and Toxin Extrusion's (MATE) role in renal organic cation secretion

描述(由申请人提供)：该项目的长期目标是确定两种相关的转运蛋白MATE1和Mate2-K在人体药物肾脏分泌中的生理作用。这一目标将通过确定(1)这两种转运体的独特底物选择性，(2)每种转运体都沿人肾近端小管的长度表达，以及(3)它们对原代培养的人肾近端小管细胞药物转运的相对影响来实现。这些实验将需要使用细胞培养、异源蛋白表达、膜转运动力学分析、转运蛋白选择性的QSAR建模、免疫组织化学和RNAi敲除原代人肾细胞天然蛋白表达的方法。掌握这些技术，以及与它们在肾脏转运生理学研究中的使用相关的培训，将有助于推动我在肾脏生理学和药物处理药理学领域的生物医学研究生涯。这项研究的结果将有助于建立底物/抑制物与人类肾脏药物转运蛋白相互作用的预测模型。这些信息可能有助于消除或减少不必要的药物相互作用。

DESCRIPTION (provided by applicant): The long-term goal of the project is to establish the physiological roles of two related transport proteins, MATE1 and MATE2-K, in the renal secretion of drugs from the human body. This goal will be approached by determining (1) the unique substrate selectivities of these two transporters, (2) where each is expressed along the length of the human renal proximal tubule, and (3) their relative influence on drug transport in primary cultures of human renal proximal tubule cells. These experiments will entail use of methods of cell culture, heterologous protein expression, kinetic analysis of membrane transport, QSAR modeling of transport protein selectivity, immunuhistochemistry, and RNAi knockdown of native protein expression in primary human renal cells. Acquiring these techniques, and the trainining associated with their use in the study of renal transport physiology, will help propel me forward to a career of biomedical research in the area of renal physiology and pharmacology of drug handling. The results of this study will assist in the development of a preditive model of substrate/inhibitor interaction with drug transporters in the human kidney. This information may help eliminate or reduce unwanted drug- drug interactions.