DIETARY CAROTENOIDS--LIPOPROTEIN CELL INTERACTIONS

膳食类胡萝卜素--脂蛋白细胞相互作用

• 批准号: 6043797
• 负责人: EARL Howard HARRISON
• 金额: $ 14.96万
• 依托单位: U.S. DEPARTMENT OF AGRICULTURE
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-07-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6043797
• 关键词: antioxidants; biological transport; blood chemistry; blood lipoprotein; blood lipoprotein metabolism; blood lipoprotein transport; carotene; carotenoids; cell line; clinical research; dietary constituent; dietary supplements; free radical oxygen; human subject; hybridomas; nutrition related tag; oxidation; oxidative stress; oxidized lipid; vascular endothelium; vitamin metabolism

DESCRIPTION: Plasma carotenoids are transported in lipoproteins and may protect them from oxidation, a process involved in atherosclerosis. When LDL was enriched with specific carotenoids only B-carotene was able to inhibit Cu-2+-mediated LDL oxidation, and its effect was modest. Thus, the protective effect of carotenoids on atherosclerosis may be unrelated to their presence as endogenous antioxidants in lipoproteins. Vascular cells can oxidize lipoproteins and carotenoids may alter their ability to do so. Metabolism of carotenoids may be necessary for their action. The proposed studies will define the mechanisms of cellular uptake and metabolism of carotenoids with particular focus on the interactions of lipoproteins and vascular endothelial cells since this may be important in atherogenesis. In aim 1 the ability of specific carotenoids to inhibit the cell-mediated oxidation of lipoproteins will be assessed. Human endothelial cell hybridomas, EaHy cells, will be used to oxidize lipoproteins. The applicant will test the hypothesis that carotenoids, either in the lipoprotein per se or delivered to the cell, inhibit the cell-mediated oxidation of lipoproteins. The molecular mechanisms of this effect will be examined by testing the hypothesis that increasing the cellular content of carotenoids decreases the production of reactive oxygen species and increases the cell's resistance to oxidative damage. In aim 2, the mechanisms of uptake of carotenoids will be determined in endothelial cells (EaHy-1), hepatoctyes (HepG2), and adipocytes (3T3-L1 cells). The applicant will test the hypothesis that cellular uptake of carotenoids is governed by the same cell-specific mechanisms involved in the uptake of other non-polar lipids. In aim 3, the products of carotenoid metabolism will be defined in order to understand the mechanisms of carotenoid action. The applicant will test the hypothesis that endothelial cell-mediated oxidation of lipoprotein carotenoids leads to the formation of epoxide products, such as those known to be formed via oxidation reactions of carotenoids in chemical systems. In this aim the applicant will also ask if EaHy cells convert carotenoids to metabolic products. The applicant will test the hypothesis that the intracellular metabolism of lipoprotein-derived carotenoids proceeds via oxidation cleavage of the chain of double bonds.

描述：血浆类胡萝卜素在脂蛋白中转运， 保护它们免受氧化，这是动脉粥样硬化的一个过程。 当 LDL富含特定的类胡萝卜素，只有B-胡萝卜素能够 抑制Cu-2+介导的LDL氧化，其作用是适度的。 因此 类胡萝卜素对动脉粥样硬化的保护作用可能与 它们作为脂蛋白中的内源性抗氧化剂存在。 血管细胞 可以氧化脂蛋白和类胡萝卜素可能会改变他们这样做的能力。 类胡萝卜素的代谢可能是其作用所必需的。 拟议 研究将确定细胞摄取和代谢的机制， 类胡萝卜素，特别关注脂蛋白的相互作用， 血管内皮细胞，因为这在动脉粥样硬化形成中可能是重要的。 在 目的1特异性类胡萝卜素抑制细胞介导的 将评估脂蛋白的氧化。 人内皮细胞 杂交瘤EaHy细胞将用于氧化脂蛋白。 申请人 将检验类胡萝卜素，无论是在脂蛋白本身， 或递送至细胞，抑制细胞介导的 脂蛋白 这种效应的分子机制将通过以下方法进行研究： 检验增加细胞内类胡萝卜素含量 减少活性氧的产生，增加细胞的 抗氧化损伤。 在目标2中， 类胡萝卜素将在内皮细胞（EaHy-1）、肝细胞（Hepatocyte）和肝细胞（Hepatocyte）中测定。 （HepG 2）和脂肪细胞（3 T3-L1细胞）。 申请人将测试 假设细胞对类胡萝卜素的摄取由相同的 参与其他非极性脂质摄取的细胞特异性机制。 在目标3中，将定义类胡萝卜素代谢的产物，以便 了解类胡萝卜素的作用机制。 申请人将测试 内皮细胞介导脂蛋白氧化假说 类胡萝卜素导致形成环氧化物产物，例如已知的那些 通过类胡萝卜素在化学体系中的氧化反应形成。 在 为了这个目的，申请人还将询问EaHy细胞是否将类胡萝卜素转化为 代谢产物 申请人将检验以下假设： 脂蛋白衍生的类胡萝卜素的细胞内代谢通过 双键链的氧化断裂。