SREBP pathway and cellular cholesterol homeostasis

SREBP 通路与细胞胆固醇稳态

• 批准号: 6910656
• 负责人: MICHAEL S BROWN
• 金额: $ 38.51万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6910656
• 关键词: active sites; blood lipoprotein metabolism; chemical cleavage; cholesterol; endoplasmic reticulum; enzyme activity; fatty acid biosynthesis; fluorescent dye /probe; genetic regulatory element; immunoelectron microscopy; intracellular transport; laboratory mouse; lipid transport; liver cells; low density lipoprotein receptor; protein degradation; protein protein interaction; protein structure; steroid biosynthesis; tissue /cell culture; transcription factor; unsaturated fatty acids

DESCRIPTION: (provided by applicant) This Project has been at the center of this Program Project Grant since its inception in 1977. The objective continues to be an understanding of the mechanism by which cells sense cholesterol and adjust its uptake via the LDL receptor pathway and its synthesis via the cholesterol biosynthetic pathway so as to maintain an optimal level of cholesterol in cell membranes. An understanding of this control mechanism may help to explain why ingestion of cholesterol and saturated fatty acids leads to an elevation of LDL in plasma and the consequent atherosclerosis. In recent years, we have learned that an understanding of the SREBP pathway has another implication, equally as important as its implication for cholesterol homeostasis. This implication derives from the evidence that SREBPs regulate the synthesis of unsaturated fatty acids as well as cholesterol. These studies therefore may increase our understanding of the disordered fatty acid synthesis that predisposes to atherosclerosis in states of obesity, insulin resistance, and diabetes mellitus.

描述：（申请人提供） 本项目自成立以来一直是本计划项目资助的中心 1977年 目标仍然是了解 细胞感知胆固醇并通过LDL受体途径调节其摄取， 通过胆固醇生物合成途径合成，以维持 细胞膜中胆固醇的最佳水平。理解本 控制机制可能有助于解释为什么摄入胆固醇和 饱和脂肪酸导致血浆中LDL升高， 随后的动脉粥样硬化。近年来，我们了解到， 对SREBP通路的理解还有另一个含义， 其重要性与其对胆固醇体内平衡的影响一样。这种含义 来源于SREBPs调节不饱和脂肪酸合成的证据， 脂肪酸和胆固醇。因此，这些研究可能会增加我们的 了解紊乱的脂肪酸合成， 肥胖、胰岛素抵抗和糖尿病状态下的动脉粥样硬化 糖尿病。