DIETARY CAROTENOIDS--LIPOPROTEIN CELL INTERACTIONS

膳食类胡萝卜素--脂蛋白细胞相互作用

• 批准号: 2605540
• 负责人: EARL Howard HARRISON
• 金额: $ 17.71万
• 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/2605540
• 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运输，可能 保护它们免受氧化，这是涉及动脉粥样硬化的过程。 什么时候 LDL富含特定的类胡萝卜素，仅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 它们作为脂蛋白中内源性抗氧化剂的存在。 血管细胞 可以氧化脂蛋白和类胡萝卜素可能会改变其这样做的能力。 类胡萝卜素的代谢可能是其作用所必需的。 提议 研究将定义细胞摄取和代谢的机制 类胡萝卜素特别关注脂蛋白和 血管内皮细胞，因为这在动脉粥样硬化中可能很重要。 在 目标1特定类胡萝卜素抑制细胞介导的能力 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 将检验以下假设，即类胡萝卜素在脂蛋白本身中要么 或递送到细胞，抑制细胞介导的氧化 脂蛋白。 该作用的分子机制将通过 测试增加类胡萝卜素细胞含量的假设 减少活性氧的产生并增加细胞的产生 抵抗氧化损伤。 在AIM 2中，吸收机制 类胡萝卜素将在内皮细胞（EAHY-1），肝细胞中确定 （HEPG2）和脂肪细胞（3T3-L1细胞）。 申请人将测试 假设类胡萝卜素的细胞摄取受相同的控制 细胞特异性机制涉及其他非极性脂质的摄取。 在AIM 3中，将定义类胡萝卜素代谢的产物，以便 了解类胡萝卜素作用的机制。 申请人将测试 内皮细胞介导的脂蛋白氧化的假设 类胡萝卜素导致形成环氧化物产品，例如已知的产品 通过类胡萝卜素在化学系统中的氧化反应形成。 在 此目标申请人还将询问EAHY细胞是否将类胡萝卜素转化为 代谢产品。 申请人将检验以下假设 脂蛋白衍生类胡萝卜素的细胞内代谢通过 双键链的氧化裂解。