CELLULAR LIPID AND LIPOPROTEIN BIOCHEMISTRY

细胞脂质和脂蛋白生物化学

• 批准号: 3942839
• 负责人: J M HOEG
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3942839
• 关键词: apolipoproteins; atherosclerosis; blood lipoprotein metabolism; cholesterol; fibroblasts; gene expression; high density lipoproteins; homeostasis; human subject; lipid metabolism; lipid transport; lipoprotein disorder; liver cells; low density lipoprotein; membrane lipids; molecular pathology; tissue /cell culture

The principal interest of this laboratory is to evaluate cellular lipoprotein and apolipoprotein metabolism. Several different human cells lines are maintained in tissue culture and the ability of cells, lipoproteins, and apolipoproteins from nomolipidemic and dyslipidemic patients are studied. Our previous investigations on receptors for low density lipoproteins and high density lipoproteins and the intracellular enzymes relevant to cellular cholesterol homeostasis (acid and neutral cholesteryl ester hydrolase, Acyl: cholesterolacyltransferase, and HMG-CoA reductase) have been extended to evaluate the coordinate regulation of these proteins in human hepatocytes and in the human hepatoma cell line HEPG2. Since the liver is a primary source of apolipoprotein synthesis as well as lipoprotein catabolism, these studies are now focused upon how these different intracellular pathways are related to nascent apolipoprotein biogenesis. Apolipoprotein synthesis is regulated at the levels of transcription and translation. In addition, several of the apolipoproteins are modified post-translationally by glycosylation, fatty acid acylation, co- and post-translational proteolytic cleavage, and by phosphorylation. Insights gained into apolipoprotein synthesis and structure-function relationships are complemented by outpatient clinical trials designed to modify apolipoprotein synthesis and secretion in hyperlipidemic patients.

该实验室的主要兴趣是评估细胞 脂蛋白和载脂蛋白代谢。 几种不同的 人类细胞系维持在组织培养物中，并且具有 来自 nomolipidemic 和的细胞、脂蛋白和载脂蛋白 对血脂异常患者进行了研究。 我们之前的调查 低密度脂蛋白和高密度脂蛋白受体 脂蛋白和与细胞相关的细胞内酶 胆固醇稳态（酸性和中性胆固醇酯 水解酶、酰基：胆固醇酰基转移酶和 HMG-CoA 还原酶）已被扩展以评估坐标 这些蛋白质在人肝细胞和肝细胞中的调节 人肝癌细胞系HEPG2。 由于肝脏是主要的 载脂蛋白合成和脂蛋白的来源 分解代谢，这些研究现在集中于这些 不同的细胞内途径与新生 载脂蛋白生物发生。 载脂蛋白合成受到调节 在转录和翻译水平上。 此外，还有几个 的载脂蛋白被翻译后修饰 糖基化、脂肪酸酰化、共翻译和翻译后 蛋白水解和磷酸化。 获得的见解 载脂蛋白合成和结构功能关系是 辅之以门诊临床试验，旨在修改 高脂血症患者的载脂蛋白合成和分泌。