NMR STUDIES OF CYTOSOLIC METAL IONS AND OXIDATIVE STRESS

细胞质金属离子和氧化应激的核磁共振研究

• 批准号: 7117822
• 负责人: Raj K Gupta
• 金额: $ 28.54万
• 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 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7117822
• 关键词: NMR; STUDIES; CYTOSOLIC; METAL; IONS

DESCRIPTION (provided by applicant): Our long-range goal is to elucidate the role of intracellular mineral ions (Na+, K+, free Mg2+ & free Ca2+) and oxidative stress in the pathophysiology of essential hypertension and type 2 diabetes. We seek to understand how the regulation of intracellular concentrations of essential metal ions and membrane lipids goes astray in health disorders, especially hypertension and diabetes. Our main research tool is NMR spectroscopy. Our laboratory played a key role in the development of NMR methods for measuring various intracellular cations and we also have considerable expertise in the use of 1H NMR for analyzing membrane phospholipid composition and the degree of membrane fatty acid unsaturation (double bonds) and average chain length. Oxidative stress, which may play a contributory role in the pathogenesis of diabetes as well as hypertension, causes peroxidative degradation of membrane lipids resulting in a loss of fatty acid double bonds that can be quantitated by 1H NMR. The following specific aims will be pursued: (1) To investigate the mechanism of altered renal sodium homeostasis in salt-sensitive hypertension; (2) To demonstrate that oxidative stress, which results in overproduction of reactive oxygen species (ROS), can cause loss of unsaturation in fatty acyl chains of membrane phospholipids as measured by 'H NMR, and to test the hypothesis that peroxidative degradation of lipids as measured by loss of membrane fatty acid unsaturation during oxidative stress results in intracellular ionic changes similar to those seen in essential hypertension; (3) To investigate a possible protective role of magnesium against oxidative stress and whether there is a decrease in antioxidant capacity, as measured by glutathione (GSH) levels, in tissues exposed to low Mg environment; (4) To test the hypothesis that a deficit in membrane fatty acid unsaturation is associated with human essential hypertension and to investigate if there is an alteration in sphingomyelin-ceramide pathway in hypertension; (5) To find out if impairment of nitric oxide synthesis by inhibition of nitric oxide synthase, which causes hypertension in a normal rat, produces membrane lipid changes similar to those seen in essential hypertension; (6) To test the hypothesis that hyperglycemia causes peroxidative degradation,of membrane lipids as measured by 1H NMR, especially in vascular tissue, and, if so, whether hyperglycemia associated loss of fatty acid unsaturation and intracellular ionic alterations can be reversed by dietary antioxidants such as vitamin C and E; (7) To investigate increased vulnerability of hypertensive as well as hyperglycemic kidney and myocardium to ischemic damage and its relationship to increased perexidative degradation of membrane lipids; and (8) To design, develop and test a method for non-invasive measurement of "intracellular sodium using triple-quantum filtered (TQ)23 Na NMR. The proposed NMR investigations of intracellular ions and oxidative stress in hypertension and hyperglycemia condition may eventually lead to better strategies for the management of these health disorders.

描述(申请人提供)：我们的长期目标是阐明细胞内矿物质离子(Na+，K+，游离镁离子和游离钙离子)和氧化应激在高血压和2型糖尿病的病理生理学中的作用。我们试图了解细胞内必需金属离子和膜脂浓度的调节在健康疾病中是如何误入歧途的，特别是高血压和糖尿病。我们的主要研究工具是核磁共振波谱。我们的实验室在开发核磁共振方法测量各种细胞内阳离子方面发挥了关键作用，我们还在使用1H核磁共振分析膜磷脂组成、膜脂肪酸不饱和度(双键)和平均链长方面拥有相当的专业知识。氧化应激可能在糖尿病和高血压的发病机制中发挥作用，导致膜脂的过氧化降解，导致脂肪酸双键的丢失，这些双键可以通过1H核磁共振进行定量。我们将致力于以下具体目标：(1)研究盐敏感型高血压肾脏钠稳态改变的机制；(2)证明氧化应激可导致膜磷脂脂肪酰链不饱和度的丢失，并验证氧化应激导致细胞内离子变化的假说，氧化应激导致的细胞内离子变化类似于高血压；(3)研究镁对氧化应激的可能保护作用，以及暴露在低镁环境中的组织中是否存在以谷胱甘肽(GSH)水平衡量的抗氧化能力下降；(4)检验膜脂肪酸不饱和缺陷与人类高血压有关的假说，并调查高血压是否存在鞘磷脂-神经酰胺途径的改变；(5)了解引起正常大鼠高血压的一氧化氮合酶(NOS)合成障碍是否会产生与高血压相似的膜脂变化；(6)测试高血糖可引起膜脂过氧化降解的假设，尤其是在血管组织中，如果是的话，是否高血糖相关的脂肪酸不饱和度的丧失和细胞内离子的改变可被饮食中的抗氧化剂如维生素C和E逆转；(7)研究高血压以及高血糖肾脏和心肌对缺血性损伤的易感性及其与膜脂过氧化降解增加的关系；以及(8)设计、开发和测试一种使用三量子过滤(TQ)23 Na核磁共振无创测量“细胞内钠”的方法。建议的核磁共振研究高血压和高血糖状态下的细胞内离子和氧化应激，最终可能导致更好的策略来管理这些健康疾病。

项目成果

The role of receptor topology in the vitamin D3 uptake and Ca(2+) response systems.

受体拓扑在维生素 D3 摄取和 Ca(2 ) 反应系统中的作用。

• DOI: 10.1016/j.bbrc.2016.06.143
• 发表时间: 2016
• 期刊: Biochemical and biophysical research communications
• 影响因子: 3.1
• 作者: Morrill,GeneA;Kostellow,AdeleB;Gupta,RajK
• 通讯作者: Gupta,RajK

In vitro human leukocyte labeling with (64)Cu: an intraindividual comparison with (111)In-oxine and (18)F-FDG.

• DOI: 10.1016/j.nucmedbio.2009.03.001
• 发表时间: 2009-07
• 期刊: NUCLEAR MEDICINE AND BIOLOGY
• 影响因子: 3.1
• 作者: Bhargava, Kuldeep K.;Gupta, Raj K.;Nichols, Kenneth J.;Palestro, Christopher J.
• 通讯作者: Palestro, Christopher J.