NHLBI MINORITY INSTITUTION FACULTY MENTORED RESEARCH

NHLBI 少数族裔机构教员指导研究

• 批准号: 6056083
• 负责人: Harpal Singh
• 金额: $ 9.51万
• 依托单位: SAVANNAH STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6056083
• 关键词: blood toxicology; carbopolycyclic compound; erythrocyte membrane; erythrocytes; glucose 6 phosphate; hemolytic anemia; hemotoxin; human subject; laboratory rat; minority institution research support

DESCRIPTION (Adapted from applicant's abstract) This application requests support for a minority school faculty development award. Training is to be undertaken in the Department of Cell and Molecular Pharmacology at the Medical University of South Carolina and will consist of attendance at departmental research seminars, tutorials, course work and a research project. One summer and one quarter per year will be devoted to the project. The proposed research will be undertaken in the laboratory of Dr. David Jollow, and will be concerned with the an aspect of the mechanisms underlying the hemolytic anemia that occurs in man and animals in response to arylamine drugs and environmental chemicals. Ongoing research in Dr. Jollow's labora-tory has indicated that: a) the hemotoxicity is due to the action(s) of metabolites (i.e., aryl hydroxylamine derivatives of the parent arylamines) rather than the parents compounds; b) that the hemolytic activity is associated with the formation of mixed protein-protein disulfides between hemoglobin and the skeletal proteins of the red cell; which c), appear to arise secondary to hydroxylamine-induced radical generation within the red cell. The chemical nature of the "primary" radicals is uncertain. The proposed studies will investigate one sub-hypothesis; viz, that the primary hemotoxin radical is the hydronitroxide derivative of the arylhydroxylamine. Specifically, a series of structurally related aryl hydroxylamines (selected on the basis of varying arylhydronitroxide stability), will be compared with respect to aryl hydronitroxide (selected on the basis of varying arylhydro-nitr-oxide stability), will be compared with respect to their hemolytic potency, methemoglobinemic activity, chemical stability and effect on red cell membrane skeletal proteins. It is expected that these studies will lead to a detailed exploration of the biology of the red cell and red cell membrane, as well as extensive experience with the experimental approaches needed to examine the relationship between membrane structure and function in blood cells. Of importance, the experience gained in basis studies or rat red cells in the mentor's laboratory (aims 1 and 2) will lead to studies in normal and glucose-6-phosphate deficient (A-) human red cells (aims 3) at the applicant's institution. This research plan is designed to expose the applicant to all facets of the experimental design and general approach to studies on the molecular basis of chemical-induced tissue injury. While the specific experiments are focused on hemolytic anemia as an endpoint, the approach is a general one which will equip the P.I. for a wide range of cardiovascular/environmental research.

描述 (改编自申请人的摘要)本申请请求支持 少数民族学校教师发展奖。培训将在#年进行 医科大学细胞与分子药理学系 南卡罗来纳州，将包括参加部门研究 研讨会、教程、课程作业和一个研究项目。一个夏天和一个夏天 每年每季度将专门用于该项目。 拟议的研究将在大卫博士的实验室进行。 Jollow，并将关注机制的一个方面 在人和动物中发生的溶血性贫血的潜在反应 芳胺类药物和环境化学品。正在进行的研究在Dr。 Jollow的实验室表明：a)血液毒性是由于 代谢物(即母体的芳基羟胺衍生物)的作用(S) 芳胺)而不是父母的化合物；b)溶血剂 活性与混合蛋白质-蛋白质的形成有关 血红蛋白和红细胞骨架蛋白之间的二硫键； 其中c)似乎继发于羟胺诱导的自由基。 在红血球内生成。“初级”的化学性质 激进分子是不确定的。拟议的研究将调查一项 次要假设；即，主要的血球毒素自由基是 芳基羟胺的氢硝基衍生物。具体地说，一系列 结构上相关的芳基羟胺(根据 不同的芳基氢氧化氮稳定性)，将与芳基进行比较 氢氧化亚氮(根据不同的芳基氢氧化氮选择 稳定性)，将与它们的溶血效力进行比较， 高铁血红蛋白的活性、化学稳定性及其对红细胞的影响 膜骨架蛋白。预计这些研究将导致 对红血球和红细胞膜的生物学进行详细的探索， 以及在实验方法方面的丰富经验 检测血液中膜结构与功能的关系 细胞。重要的是，在基础研究或老鼠红中获得的经验 导师实验室中的细胞(目标1和2)将导致在 正常和葡萄糖-6-磷酸缺乏(A-)人红细胞(AIMS 3) 申请人所在的机构。 这项研究计划旨在使申请者接触到 分子基础研究的实验设计和一般方法 由化学物质引起的组织损伤。虽然具体的实验是 该方法以溶血性贫血为终点，是一种一般性的方法。 这将为P.I.配备广泛的心血管/环境 研究。