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PTERIDINE METABOLISM AND TRANSPORT IN MALIGNANT CELLS

恶性细胞中蝶啶的代谢和转运

基本信息

批准号：
3177218
负责人：
STEPHANIE WEBBER
金额：
$ 9.79万
依托单位：
SCRIPPS CLINIC AND RESEARCH FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
1985
资助国家：
美国
起止时间：
1985-02-01 至 1988-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3177218
关键词：
density gradient ultracentrifugation dihydrofolate reductase erythroleukemia extracellular fluorimetry folate human tissue lymphocyte lymphocytic leukemia myelogenous leukemia neoplastic cell neoplastic cell culture for noncancer research oxidoreductase inhibitor pteridines radiotracer secretion spectrometry

项目摘要

Clinical observations have linked altered pteridine metabolism and enhanced excretion of pteridines to diseases, which include malignancies, viral infections, generalized activation of the cellular immune system, and AIDS. In order to help understand these observations, this proposal seeks to investigate certain areas of pteridine biochemistry in human cell systems. In particular, it is intended to determine the pteridine content of cell extracts and culture media; to investigate the properties of the transport system which controls the influx and efflux of these derivatives; and to determine the relative roles played by dihydropteridine and dihydrofolate reductases in controlling pteridine metabolism. The investigations will be carried out using human lymphocytes and a variety of malignant cell lines of human origin including CEM, WIL2, HL60, and K562. The enzyme studies will employ the isolated proteins from rat liver and human sources. Of particular importance will be the identification of pteridines subject to modulated excretion. Radioactively labelled pteridines and folates will be employed to establish the origin of the secreted compounds since intermediates of both pteridine biosynthesis or folate degradation could be involved. The properties of the pteridine transport system will illustrate whether these provide a clearer picture of whether the pteridine excretion products of certain cell systems might be of regulatory significance by uptake or surface binding to other cell types. By these means, it is intended to expand the understanding of pteridine function in human cell systems and, thereby, determine whether previously documented clinical observations can be exploited either diagnostically or therapeutically. (A)

临床观察发现蝶啶代谢的改变与增强蝶啶对疾病的排泄，包括恶性肿瘤、病毒性疾病感染、细胞免疫系统的普遍激活，以及艾滋病。为了帮助理解这些观察结果，本提案寻求研究人体细胞中蝶啶生物化学的某些领域系统。特别是，旨在测定蝶啶含量细胞提取物和培养基；来调查的属性控制这些衍生物流入和流出的运输系统；并确定二氢蝶啶和二氢叶酸还原酶控制蝶啶代谢。这将使用人类淋巴细胞和各种人类来源的恶性细胞系，包括 CEM、WIL2、HL60 和 K562。酶研究将采用从大鼠肝脏中分离出的蛋白质人力资源。特别重要的是确定蝶啶受调节排泄。放射性标记将使用蝶啶和叶酸来确定由于蝶啶生物合成的中间体或可能涉及叶酸降解。蝶啶的性质运输系统将说明这些是否可以提供更清晰的情况某些细胞系统的蝶啶排泄产物是否可能是通过摄取或与其他细胞表面结合具有调节意义类型。通过这些方式，旨在扩大对蝶啶在人类细胞系统中的功能，从而确定是否可以利用以前记录的临床观察结果诊断或治疗。（一个）