RENAL TUBULAR TRANSPORT OF BENCE JONES PROTEINS

Bence Jones 蛋白质的肾管转运

• 批准号: 3447319
• 负责人: PETER SMOLENS
• 金额: $ 4.97万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 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/3447319
• 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

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.

蛋白质的肾小管运输被认为是通过内吞作用发生的。在……里面 在这个过程中，蛋白质被识别，结合到刷子的边缘 膜，并内化在囊泡中。重要的因素 用于识别、结合和内化各种蛋白质 由肾脏处理的是不完全了解的。此外, 定量评价肾脏对过滤蛋白的吸收能力 对相对较少的蛋白质是可用的。肾小管容量和肾小管容量 尤其是对本斯-琼斯蛋白的吸收亲和力很差。 已定义。 在本研究中，一组四个同源kappa的肾小管处理 轻链(Bence Jones蛋白质)将用 大鼠浅层肾单位的活体肾小管微灌注。这其中的每一个 蛋白质的净电荷与等电点不同。 从4.3到7.6不等。这些由免疫细胞瘤合成的蛋白质 植入老鼠体内，在尿液中收集，分离，并进行放射性标记 带着125i。利用微穿孔技术，125I轻链被灌流 进入小管段的一端。在另一端，灌流液是 收集的~(125)I-轻链在整个长度上的吸收量 线段已确定。小管的亲和力和能力 吸收每个不同电荷的轻链将在下面进行评估 不同轻链载荷的条件。联合输注丙种球蛋白的效果 其他轻链，以及输液氨基酸组成的变化 还将检查这些蛋白质的吸收情况。 将分析不同轻链的吸收大小 为了了解：1)它们是否相似或不同，b)他们建议 吸收是受体介导的，c)电荷限制似乎是 很重要。将进行形态研究，以确定不同的 带电荷的蛋白质结合到管腔上的不同位置 膜，如果它们以不同的方式内化，如果暴露在 这些轻链上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理解这种机制 通过它进行肾小管蛋白的运输。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蛋白可能在临床上具有重要意义 评估多发性骨髓瘤患者。