PROCESSING OF HUMAN PRORENIN

人肾素原的加工

• 批准号: 3236707
• 负责人: Willa A Hsueh
• 金额: $ 15.1万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-05-01 至 1992-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3236707
• 关键词: affinity chromatography; chorioallantoic membrane; complementary DNA; enzyme inhibitors; gel electrophoresis; gel filtration chromatography; gene expression; high performance liquid chromatography; human tissue; kallikreins; kidney; pepsin; peptidases; pregnancy toxemia /hypertension; protein sequence; protein structure; proteolysis; radioimmunoassay; renal hypertension; renin; tissue /cell culture; trypsin

More than half of the circulating renin in man exists as an inactive form. Mounting evidence suggests inactive renin is the biosynthetic precursor of renin, i.e. prorenin. Our hypothesis is that 1) conversion of prorenin to renin participates in the regulation of renin production, 2) this conversion is mediated by limited proteolysis involving specific processing enzymes, and 3) various tissues in the body have different capabilities in accomplishing this conversion. Our specific objectives are to 1) purify expressed human prorenin, 2) use purified prorenin to develop assays for the processing enzyme that converts proenin to renin, 3) study in vivo and in vitro activation of expresses prorenin, and 4) purify the renin processing enzyme from human kidney. The long-term goal will be to determine whether conversion of prorenin to renin is a regulatory step in renin production. Ultimately, we hope to determine whether control or renin processing could be used to correct renin deficiency or excess states in man, such as the syndrome of hyporeninemic hypoaldosteronism or such as high and normal renin essential hypertension. Control of the processing enzyme may prove to be a new means to regulate hormone and enzyme production.

人体中超过一半的循环肾素以 非活动形式。 越来越多的证据表明，非活性肾素是 肾素的生物合成前体，即肾素原。 我们的假设是 1) 肾素原向肾素的转化参与 肾素产生的调节，2）这种转化是由 涉及特定加工酶的有限蛋白水解，以及 3) 体内不同的组织具有不同的能力 完成这个转换。 我们的具体目标是 1) 纯化表达的人肾素原， 2) 使用纯化的肾素原来开发处理分析方法 将 proenin 转化为肾素的酶，3) 体内和体内研究 体外激活肾素原表达，4) 纯化肾素 来自人类肾脏的加工酶。 长期目标将 确定肾素原向肾素的转化是否是 肾素产生的调节步骤。 最终，我们希望 确定对照或肾素处理是否可用于 纠正人体肾素缺乏或过剩的状态，例如 低肾素血症性低醛固酮增多症或高、低醛固酮症等综合征 肾素正常的原发性高血压。 加工控制 酶可能被证明是调节激素和激素的新手段 酶的生产。