NMR STUDIES OF METAL IONS IN INTACT CELLS AND TISSUES

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(钠、钾、镁、钙)在细胞增殖中的作用 分化，以及各种细胞过程中的激素调节。 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，以及这种调节是如何进行的 在癌症、糖尿病、镰状细胞疾病等疾病中误入歧途 高血压，包括由铅中毒引起的。我们的研究工具是 核磁共振波谱。我们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手术标本。特定的 要追求的目标是：(1)检查促有丝分裂刺激是否 淋巴细胞体外增殖伴随着Na+的增加 质膜通透性的变化；(2)研究不同剂量黄连提取物对细胞质膜通透性的影响 糖尿病对大鼠心肌细胞内钠离子、游离钙离子和pH的影响 肾组织；(3)建立核磁共振可见Na+的变化 与非肿瘤组织相比，在肿瘤组织中发生 确定肿瘤的良、恶性分支是否可以区分 根据它们的细胞内Na+浓度：(4)测试 假设细胞内游离镁离子和pH的下降，以及 核磁共振可见胞内Na+和游离钙离子的增加与 (5)细胞外镁离子对高血压的影响。 心肌细胞内离子和心脏生物能量学； 探讨细胞内Na+和游离钙在其发病机制中的作用 并检验一种假设，即一种原发性高血压 铅中毒在细胞水平的损害是细胞的一种扰动 钠稳态；(7)表征Na~+、K~+离子在体内的状态 氧合和脱氧状态下的正常和镰刀状红细胞 (8)测定组织间隙中Na+的核磁共振可见度 双量子过滤~(23)Na核磁共振技术的发展 选择性检测完整灌流器官细胞内Na+ 顺磁性试剂来抑制细胞外信号。

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.