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RENAL TUBULAR TRANSPORT OF BENCE JONES PROTEINS

Bence Jones 蛋白质的肾管转运

基本信息

批准号：
3447320
负责人：
PETER SMOLENS
金额：
$ 4.95万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-12-01 至 1987-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3447320
关键词：
brush border membrane disease /disorder model gel filtration chromatography genetic strain histochemistry /cytochemistry ion exchange chromatography isoelectric point kidney metabolism membrane activity multiple myeloma neoplasm /cancer immunology neoplasm /cancer transplantation perfusion radiotracer receptor mediated endocytosis renal tubular transport urinalysis

项目摘要

Renal tubular transport of proteins is felt to occur by endocytosos. In this process, the protein is recognized, bound to the brush border membrane, and internalized in a vesicle. The factors which are important for recognition, binding, and internalization of the various proteins handled by the kidney are incompletely understood. In addition, quantitative evaluation of the renal capacity to absorb filtered proteins is available for relatively few proteins. The renal tubular capacity and affinity for absorption of Bence Jones proteins, in particular, is poorly defined. In this study, renal tubular handling of a group of four homologous kappa light chains (Bence Jones proteins) will be examined with the technique of in vivo tubular microperfusion in rat superficial nephrons. Each of these proteins has a different net electric charge with isoelectric points ranging from 4.3 to 7.6. These proteins, synthesized by immunocytomas implanted in rats, are collected in the urine, isolated, and radiolabelled with 125I. Using micropuncture techniques, 125I-light chain is perfused into one end of a tubule segment. At the other end, the perfusate is collected and the amount of 125I-light chain absorbed over the length of the segment is determined. The affinity and capacity of the tubule to absorb each of the differently charged light chains will be evaluated under conditions of varying light chain loads. The effect of co-infusion of the other light chains, and variation of the infusion amino acid composition on absorption of these proteins will also be examined. The magnitude of absorption of the different light chains will be analyzed to see if: 1) they are similar or different, b) they suggest the absorption is receptor mediated, c) electric charge constraints seem to be important. Morphologic studies will be done to see if the differently charged proteins are bound to different sites on the tubular luminal membrane, if they are internalized in different ways, and if exposure of the tuvules to these light chains induces cell toxicity. Results of this study will enable a better understanding of the mechanisms by which renal tubular protein transport takes place. Moreover, knowledge of the factors which determine the capacity and affinity of the kidney to absorb different Bence Jones proteins may be of clinical import in evaluating the patient with multiple myeloma.

蛋白质的肾小管转运被认为是通过内吞作用发生的。在在这个过程中，蛋白质被识别，膜，并内化在囊泡中。重要的因素是用于识别、结合和内化各种蛋白质肾脏的功能还不完全清楚。此外，本发明还提供了一种方法，定量评价肾脏吸收滤过蛋白的能力对相对较少的蛋白质是有效的。肾小管容量和特别是，对Bence Jones蛋白的吸收的亲和力很差，定义了在这项研究中，肾小管处理一组四个同源kappa 轻链（Bence Jones蛋白）将用以下技术进行检查：在体大鼠浅表肾单位肾小管微灌注这一切成功都蛋白质具有不同的净电荷，从4.3到7.6。这些由免疫细胞瘤合成的蛋白质植入大鼠体内，收集尿液，分离并进行放射性标记 125 i的使用微穿刺技术，灌注125 I-轻链进入小管的一端在另一端，灌注液收集的125 I-轻链的量，确定段。肾小管的亲和力和能力，吸收每个不同电荷的轻链将在不同轻链负载的条件。共输注的效果其他轻链，以及输注氨基酸组成的变化，还将检查这些蛋白质的吸收。将分析不同轻链的吸收幅度看看：1）它们是相似的还是不同的，B）它们表明吸收是受体介导的，c）电荷约束似乎是重要. 将进行形态学研究，以确定带电荷的蛋白质结合到肾小管管腔上的不同位点，膜，如果它们以不同的方式内化，如果暴露于这些轻链的小管诱导细胞毒性。这项研究的结果将使我们能够更好地了解机制肾小管蛋白质通过其转运。此外，知识决定肾脏的能力和亲和力的因素，吸收不同的Bence Jones蛋白可能具有临床意义，评估多发性骨髓瘤患者。