Lipid Peroxidation Analytical Core

脂质过氧化分析核心

• 批准号: 10327713
• 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/10327713
• 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; Metabolism; Modification; N-methylacetamide-oxotremorine M; Participant; Phenols; 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项目总结 本项目的总体目标是测试高密度脂蛋白（HDL）变化的贡献 在人类疾病中的作用，特别是动脉粥样硬化。其中一个主要的假设是， 在增加动脉粥样硬化风险的各种情况下发生的过氧化作用（例如家族性 高胆固醇血症和慢性肾病）导致HDL被活性脂质修饰 这些修饰显著改变HDL功能。这个核心将提供合成版本 向项目研究人员提供这些反应性二羰基化合物，以便他们可以测试高密度脂蛋白修饰的效果。这 核心还将提供合成化合物，作为二羰基清除剂，可用于 培养的细胞，在动物和人类中，以阻止二羰基与蛋白质的反应， 磷脂酰乙醇胺这些清除剂可用于测试这些二羰基化合物的贡献， 作为潜在的药物。最后，该核心将测量蛋白质上的二羰基加合物， 磷脂酰乙醇胺 目的1：合成IsoLG和其他二羰基化合物，用于培养细胞和动物模型的测试。 目的2：合成二羰基清除剂，用于培养细胞和动物模型的测试。 目的3：测量二羰基修饰的蛋白质和磷脂酰乙醇胺的量， 在动物模型和人类疾病的组织样本和液体中形成。