DIETARY CAROTENOIDS--LIPOPROTEIN CELL INTERACTIONS

描述：血浆类胡萝卜素通过脂蛋白运输，可能 保护他们免受氧化，这是一个涉及动脉粥样硬化的过程。什么时候 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 抑制铜-2介导的低密度脂蛋白氧化，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 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它们这样做的能力。 类胡萝卜素的代谢可能是它们发挥作用所必需的。建议数 研究将确定细胞摄取和代谢的机制 类胡萝卜素，特别关注脂蛋白和类胡萝卜素的相互作用 血管内皮细胞，因为这可能在动脉粥样硬化形成中起重要作用。在……里面 目的1特定的类胡萝卜素抑制细胞介导的 将对脂蛋白的氧化进行评估。人内皮细胞 杂交瘤，即EaHy细胞，将被用来氧化脂蛋白。申请人 将检验类胡萝卜素的假设，无论是在脂蛋白本身中 或传递到细胞，抑制细胞介导的氧化 脂蛋白。这种效应的分子机制将通过以下方式进行研究 检验增加细胞中类胡萝卜素含量的假设 减少活性氧的产生，增加细胞的 抗氧化性损伤。在目标2中，摄取 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)。申请者将测试 假设细胞对类胡萝卜素的摄取受相同的 细胞特有的机制参与了其他非极性脂的吸收。 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。申请者将测试 内皮细胞介导的脂蛋白氧化假说 类胡萝卜素导致环氧化物产物的形成，如已知的 通过化学体系中类胡萝卜素的氧化反应而形成。在……里面 为了达到这个目的，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。申请人将检验这一假设 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.