BIOCHEMICAL GENETICS OF CELLULAR CHOLESTEROL METABOLISM

细胞胆固醇代谢的生化遗传学

• 批准号: 3241249
• 负责人: MICHAEL S SINENSKY
• 金额: $ 24.61万
• 依托单位: ELEANOR ROOSEVELT INST FOR CANCER RES
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1994-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3241249
• 关键词: HMG coA reductases; cell components; cholesterol; cholesterol oxide; density gradient ultracentrifugation; epoxides; genetic transcription; hydroxycholesterols; laboratory rat; lanosterol; liver cells; liver metabolism; molecular genetics; mutant; oxysteroid; steroid biosynthesis; steroid metabolism; tissue /cell culture; transfection

Defective regulation of serum cholesterol levels plays a critical role in the development of atherosclerosis, the leading cause of mortality in the United States. Regulation of cellular and organismic cholesterol homeostasis has been hypothesized to involve one or more oxygenated sterols which act as a signal regulating a number of aspects of cholesterol metabolism including synthesis and receptor mediated clearance. In this proposal, we describe experiments utilizing a combination of molecular and somatic cell genetic techniques designed to further elucidate the mechanisms of action of oxygenated sterols on sterol metabolism in cultured mammalian cells. Experiments are also proposed to determine mechanisms of synthesis and function of epoxysterols unrelated to regulation of sterol metabolism. These latter compounds have been found to be naturally occurring in human liver and have been demonstrated to perform a vital cellular function. Finally, a series of experiments are proposed to examine the mechanisms of action of oxysterols in the regulation of hepatic cholesterol metabolism. It is anticipated that these studies will aid in the development of chemotherapeutic methods towards management of atherosclerosis as well as shedding new light on the possible function of epoxysterols.

血清胆固醇水平的缺陷调节起着至关重要的作用 在动脉粥样硬化发展中的作用，动脉粥样硬化是动脉粥样硬化的主要原因 美国的死亡率。 细胞的调节和 据推测，有机胆固醇稳态涉及 一种或多种氧化甾醇，其充当调节信号 胆固醇代谢的许多方面，包括合成和 受体介导的清除。 在这个提案中，我们描述了 experiments utilizing a combination of molecular and somatic cell 旨在进一步阐明其机制的遗传技术 含氧甾醇对培养物甾醇代谢的作用 哺乳动物细胞。 还建议进行实验以确定 与以下因素无关的环氧甾醇的合成和功能机制 甾醇代谢的调节。 后面这些化合物已被 已发现天然存在于人类肝脏中 被证明具有重要的细胞功能。 最后，一个 提出了一系列实验来检查其机制 氧固醇在肝脏胆固醇调节中的作用 代谢。 预计这些研究将有助于 开发化疗方法来管理 动脉粥样硬化以及为可能的情况提供新的线索 环氧甾醇的功能。