LEAD AND RED CELL MEMBRANE

铅和红细胞膜

• 批准号: 3250378
• 负责人: CAROL R ANGLE
• 金额: $ 5.87万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-08-01 至 1986-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3250378
• 关键词: adult human (21+); cell morphology; child (0-11); cholesterol; density gradient ultracentrifugation; environmental toxicology; erythrocyte membrane; fatty acid metabolism; hemolysis; high performance liquid chromatography; human subject; inborn metabolism disorder; ion exchange chromatography; lead poisoning; lecithin cholesterol acyltransferase deficiency; lipid biosynthesis; lipid metabolism; mass spectrometry; membrane activity; membrane lipids; nuclear magnetic resonance spectroscopy; phosphatidylcholine sterol acyltransferase; phospholipids; porphyrins; pyrimidine nucleotides; radionuclides; thin layer chromatography

This proposal investigates the multifactorial interaction of lead and the red cell membrane. It derives from the investigators' evidence that increases in blood lead to the currently acceptable maximum for children (30 ug/dl) evoke hemolysis manifest by target cells with decreases in membrane fluidity, osmotic fragility, cell survival and pyrimidine-5 feet-nucleotidase activity, and the accumulation of cytosolic pyrimidine nucleotides and their diesters, CDP choline (CDP-C) and CDP ethanolamine (CDP-E). The specific aims are: 1) Test the hypothesis that lead induced pyrimidine-5 feet-nucleotidase deficiency (PND) evokes hemolysis via accumulation in the red cell cytosol of CDP choline and CDP ethanolamine, key intermediates in the synthesis of membrane phosphoglycerides. The effect of lead, with and without secondary accumulation of CDP-C and CDP-E, will be determined on the de novo synthesis of membrane phospholipids by the reticulocyte and the kinetics of membrane phospholipid turnover and repair by mature red cells. 2) Test the hypothesis that the effects of lead on red cell metabolism are distinct from those of PND and lead-induced PND by 31P NMR studies of MgATP, glycolytic intermediates and intracellular pH. 3) Investigate the effect of lead and lead-induced PND on lecithin acyltransferase and the phospholipid:cholesterol ratio of the red cell membrane and test the hypothesis that these are the result, not the cause, of the altered surface area/volume ratio of the red cells on lead exposure. The studies will be conducted on human red cells from normal subjects, lead workers and children with undue lead exposure. Mechanistic studies will utilize the rabbit model. The functional and biochemical changes of the red cell membrane will be correlated with 4 corroborative indices of lead exposure: blood lead, red cell lead, fluorescent erythrocyte protoporphyrins and pyrimidine-5 feet-nucleotidase of the red cell cytosol.

本研究探讨了铅与铅的多因子相互作用

项目成果

Prediction of blood lead by HPLC assay of erythrocyte pyrimidine 5'-nucleotidase.

通过红细胞嘧啶 5-核苷酸酶的 HPLC 测定预测血铅。

• DOI: 10.1093/jat/11.1.39
• 发表时间: 1987
• 期刊: Journal of analytical toxicology
• 影响因子: 2.5
• 作者: Cook,LR;Angle,CR;Kubitschek,CE;Stohs,SJ
• 通讯作者: Stohs,SJ

Erythrocyte membrane microviscosity and phospholipid composition in lead workers.

铅工红细胞膜微粘度及磷脂组成。

• DOI: 10.1136/oem.44.12.841
• 发表时间: 1987
• 期刊: British journal of industrial medicine
• 作者: Cook,LR;Stohs,SJ;Angle,CR;Hickman,TI;Maxell,RC
• 通讯作者: Maxell,RC

Erythrocyte arginase, pyrimidine 5'-nucleotidase (P5N), and deoxypyrimidine 5'-nucleotidase (dP5N) as indices of lead exposure.

红细胞精氨酸酶、嘧啶 5-核苷酸酶 (P5N) 和脱氧嘧啶 5-核苷酸酶 (dP5N) 作为铅暴露指标。

• DOI: 10.1136/oem.43.6.387
• 发表时间: 1986
• 期刊: British journal of industrial medicine
• 作者: Cook,LR;Angle,CR;Stohs,SJ
• 通讯作者: Stohs,SJ