DIETARY CAROTENOIDS--LIPOPROTEIN CELL INTERACTIONS

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，这是动脉粥样硬化的一个过程。 当 低密度脂蛋白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，其作用不大。 因此， 类胡萝卜素对动脉粥样硬化的保护作用可能与以下因素无关： 它们作为脂蛋白中的内源抗氧化剂的存在。 血管细胞 可以氧化脂蛋白，而类胡萝卜素可能会改变它们的氧化能力。 类胡萝卜素的代谢可能是其作用所必需的。 拟议的 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和 血管内皮细胞，因为这可能在动脉粥样硬化形成中很重要。 在 目标 1 特定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 将检验类胡萝卜素的假设，无论是在脂蛋白本身中 或递送至细胞，抑制细胞介导的氧化 脂蛋白。 这种效应的分子机制将通过 检验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 抵抗氧化损伤。 在目标 2 中，吸收机制 将测定内皮细胞 (EaHy-1)、肝细胞中的类胡萝卜素 （HepG2）和脂肪细胞（3T3-L1 细胞）。 申请人将测试 假设细胞对类胡萝卜素的摄取受相同的控制 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产物，以便 了解类胡萝卜素的作用机制。 申请人将测试 假设内皮细胞介导的脂蛋白氧化 类胡萝卜素导致环氧化物产物的形成，例如那些已知的 通过化学系统中类胡萝卜素的氧化反应形成。 在 为此，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。

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.