NMR STUDIES OF METAL IONS IN INTACT CELLS AND TISSUES

完整细胞和组织中金属离子的核磁共振研究

• 批准号: 3230498
• 负责人: Raj K Gupta
• 金额: $ 22.06万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-05-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3230498
• 关键词: antineoplastics; bioenergetics; biological signal transduction; cell differentiation; cell membrane; diabetes mellitus; drug adverse effect; electrophysiology; erythrocytes; heart cell; homeostasis; hormone regulation /control mechanism; human tissue; hypertension; ion transport; laboratory rat; leukocyte activation disorder; lymphocyte; lymphocyte proliferation; magnesium; membrane transport proteins; molecular pathology; nuclear magnetic resonance spectroscopy; pharmacokinetics; respiratory oxygenation

A primary goal of our research is to understand possible regulatory role of metal ions (Na+, K+, Mg2+ & Ca2+) in cellular proliferation, differentiation, and in hormonal regulation of various cellular processes. We seek also to understand how the concentrations of intracellular ions are managed by various membrane transport processes, and how such regulation goes astray in disorders such as cancer, diabetes, sickle cell disease and in hypertension, including that due to lead toxicity. Our research tool is NMR spectroscopy. Cells and tissues to be used in our research include human blood cells, rat kidney and heart cells, intact rat heart and kidney, and surgical specimens of non-neoplastic and neoplastic human tissue. Specific aims to be pursued are: (1) To examine if the mitogenic stimulation of lymphocyte proliferation in vitro is accompanied by an increase in Na+ permeability of the plasma membrane; (2) To investigate the effects of diabetes mellitus upon intracellular Na+, free Ca2+ and pH, in rat heart and kidney tissue; (3) To establish that an alteration in NMR- visible Na+ occurs in the neoplastic tissue in comparison to non-neoplastic tissue and to determine if benign and malignant fors of neoplasia can be distinguished on the basis of their intracellular Na+ concentration: (4) To test the hypothesis that a decrease in intracellular free Mg2+ and pH, along with an increase in NMR visibile intracellular Na+ and free Ca2+, is associated with essential hypertension; (5) To study the effects of extracellular Mg2+ on the intracellular ions in heart cells and on cardiac bioenergetics; (6) To investigate the role of intracellular Na+ and free calcium in the mechanism of lead-induced hypertension and to test the hypothesis that a primary lesion in lead toxicity at the cellular level is a perturbation of cellular sodium homeostasis; (7) To characterize the state of Na+ and K+ ions in normal and sickle red blood cells in oxygenated and deoxygenated states: and (8) To determine the NMR-visibility of Na+ in the interstitial spaces and to develop the technique of double quantum-filtered 23 Na NMR for the selective detection of intracellular Na+ in intact perfused organs using a paramagnetic reagent to quench the extracellular signal.

我们研究的一个主要目标是了解可能的调节作用 金属离子（Na+、K+、Mg 2+和Ca 2+）在细胞增殖中的作用， 分化，以及各种细胞过程的激素调节。 我们还试图了解细胞内离子的浓度是如何 由各种膜运输过程管理，以及这种调节如何 在癌症、糖尿病、镰状细胞病等疾病中误入歧途， 高血压，包括铅中毒。我们的研究工具是 核磁共振波谱法。在我们的研究中使用的细胞和组织包括人类 血细胞、大鼠肾脏和心脏细胞、完整的大鼠心脏和肾脏，以及 非肿瘤性和肿瘤性人体组织的手术标本。具体 目的是：（1）检查是否有促有丝分裂的刺激， 体外淋巴细胞增殖伴随着Na+的增加 （2）研究不同浓度的葡萄糖、葡萄糖、葡萄糖和葡萄糖对细胞膜通透性的影响。 糖尿病对大鼠心脏细胞内Na+、游离Ca ~（2+）和pH的影响， 肾组织;（3）确定核磁共振谱的变化-可见Na+ 与非肿瘤组织相比发生在肿瘤组织中， 以确定是否可以区分良性和恶性肿瘤 根据细胞内Na+浓度：（4）检测细胞内Na+浓度， 假设细胞内游离Mg 2+和pH的降低，沿着 NMR可见细胞内Na+和游离Ca 2+的增加与 （5）研究细胞外Mg ~（2+）对原发性高血压的影响。 心脏细胞内离子和心脏生物能量学;（6） 探讨细胞内Na+和游离钙离子在此机制中的作用 并检验一个假设，即原发性高血压 铅毒性在细胞水平上的损害是细胞内 （7）研究了不同浓度的Na ~+和K ~+在不同温度下的变化情况， 处于氧合和脱氧状态的正常和镰状红细胞：和 (8)确定间隙中Na+的NMR可见性， 发展双量子过滤23 Na核磁共振技术 使用选择性检测完整灌注器官中的细胞内Na+ 顺磁性试剂以淬灭细胞外信号。