LEAD AND RED CELL MEMBRANE

这项建议调查了铅和铅的多因素交互作用 红细胞膜。根据调查人员的证据， 血液的增加导致儿童达到目前可以接受的最大限度 (30ug/dl)可引起靶细胞明显的溶血反应 膜流动性、渗透脆性、细胞存活率与嘧啶-5 足部核苷酸酶活性与胞内嘧啶的积累 核苷酸及其二酯，CDP胆碱(CDP-C)和CDP乙醇胺 (CDP-E)。具体目的是：1)检验铅诱导的假说 嘧啶-5英尺核苷酸酶缺乏症(PND)通过 CDP胆碱和CDP乙醇胺在红细胞胞浆中的积聚， 膜磷酸甘油酯合成中的关键中间体。这个 铅的影响，有和没有CDP-C和CDP-E的二次积累， 将在膜磷脂从头合成过程中被确定 网织红细胞与膜磷脂周转动力学 由成熟的红细胞修复。2)检验以下假设： 铅对红细胞代谢的影响有别于PND和铅诱导的红细胞代谢 镁-三磷酸腺苷、糖酵解中间体和胞内PND的31P核磁共振研究 PH值。3)研究铅及其诱导的PND对卵磷脂的影响 酰基转移酶与红细胞磷脂/胆固醇比值 膜和测试假设，这些是结果，而不是原因， 铅上红细胞的表面积/体积比的变化 曝光。这些研究将在正常人的红细胞上进行。 受试者、铅工作人员和过度铅暴露的儿童。机械论 研究将利用兔子模型。功能和生化 红细胞膜的变化将与4个佐证相关 铅暴露指标：血铅、红细胞铅、荧光 红血球原卟啉与嘧啶-5英尺核苷酸酶 细胞胞浆。

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.