Lipid Peroxidation Analytical Core

脂质过氧化分析核心

• 批准号: 10544053
• 负责人: SEAN Stephen DAVIES
• 金额: $ 24.65万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10544053
• 关键词: Animal Model; Animals; Atherosclerosis; Biological; Blood; Cell model; Chemicals; Chronic Kidney Failure; Cultured Cells; Disease; Ensure; F2-Isoprostanes; Familial Hypercholesterolemia; Functional disorder; Goals; Half-Life; High Density Lipoproteins; Human; Individual; Instruction; Investigation; Lipid Peroxidation; Lipids; Liquid substance; Lysine; Malondialdehyde; Measurement; Measures; Medicine; Metabolism; Modification; Participant; Phosphatidylethanolamine; Post-Translational Protein Processing; Proteins; Pyridoxamine; Reaction; Reagent; Research Personnel; Rheumatoid Arthritis; Role; Sampling; Testing; Tissue Sample; Tissues; Vitamin B6; adduct; analog; atherosclerosis risk; experimental study; human disease; in vivo; instrumentation; methyl group; programs; small molecule

CORE C PROJECT SUMMARY The overall goal of this program project is to test the contribution of changes in high density lipoprotein (HDL) function in human disease, specifically atherosclerosis. One of the major hypotheses tested is that the lipid peroxidation that occurs during various condition that increase the risk for atherosclerosis (e.g. familial hypercholesterolemia and chronic kidney disease) causes HDL to become modified by reactive lipid dicarbonyls and that these modifications markedly alter HDL function. This core will provide synthetic versions of these reactive dicarbonyls to project investigators so that they can test the effects of HDL modification. This core will also provide synthetic compounds that act as dicarbonyl scavengers and that can be used in both cultured cells, in animals, and in humans to block the reaction of dicarbonys with proteins and phosphatidylethanolamine. These scavengers are useful both to test the contribution of these dicarbonyls and as potential medicinal agents. Finally, this core will measure dicarbonyl adducts on proteins and phosphatidylethanolamine. Aim 1: Synthesize IsoLG and other dicarbonyls for testing in cultured cell and animal models. Aim 2: Synthesize dicarbonyl scavengers for testing in cultured cell and animal models. Aim 3: Measure the amounts of dicarbonyl modified proteins and phosphatidylethanolamines that are formed in tissue samples and fluids in animal models and humans with disease.

核心C项目摘要 该计划项目的总体目标是测试高密度脂蛋白（HDL）变化的贡献 人类疾病的功能，特别是动脉粥样硬化。测试的主要假设之一是脂质 在各种情况下发生的过氧化，增加了动脉粥样硬化的风险（例如家族性 高胆固醇血症和慢性肾脏疾病）导致HDL通过反应性脂质变化 DiCarbonyls和这些修饰显着改变了HDL函数。该核心将提供合成版本 在这些反应性的二苯二苯丙基对研究人员的投影，以便它们可以测试HDL修饰的效果。这 核心还将提供合成化合物，用作DiCarbonyl清除剂，并且可以在两者中使用 培养的细胞，动物和人类中，以阻止双核与蛋白质和蛋白质的反应 磷脂酰乙醇胺。这些清除剂对于测试这些dicarbonyls的贡献和 作为潜在的药剂。最后，该核心将测量蛋白质和 磷脂酰乙醇胺。 AIM 1：合成ISLEG和其他二骨偶像在培养的细胞和动物模型中进行测试。 AIM 2：合成双骨清除剂，用于在培养的细胞和动物模型中进行测试。 AIM 3：测量甲撇剂修饰的蛋白质和磷脂酰乙醇胺的量 在动物模型和患有疾病的人类的组织样品和流体中形成。