胆固醇代谢调控的研究进展
| 作者: |
1李天平,
1轩贵平,
2庹勤慧
1 南华大学药物药理研究所， 湖南 衡阳 421001 2 南华大学药物药理研究所， 湖南 衡阳 421001； 湖南中医药大学药学院药理教研室， 长沙 410208 |
| 通讯: |
庹勤慧
Email: qhtuo@yahoo.com.cn |
| DOI: | 10.3978/j.issn.2095-6959.2014.01.012 |
| 基金: | 国家自然科学基金;湖南省高校创新平台开放基金项目;湖南省自然科学基金, 30971267，31371161，81173047;12K096;14JJ1024 |
摘要
胆固醇的合成、分解及逆向转运与动脉粥样硬化密切相关。叉头转录因子的O亚型3(fork head box O3，FoxO3)/去乙酰化酶6复合物(Sirt6 complex)、3β-脱氢胆固醇-Δ24还原酶(3β-hydroxysterol ∆(24)-reductase，DHCR24， Seladin-1)和死亡结构域相关蛋白(death domain associated protein，Daxx)可以通过调控核转录激活因子-甾醇调节元件结合蛋白(sterol regulatory element-binding proteins，SREBPs)的表达和活化来调节胆固醇合成限速酶[如3-羟基3-甲基戊二酰辅酶A还原酶(3-hydroxy-3-methylglutaryl-coenzyme A reductase， HMGCR)]等的转录，最终调控胆固醇的合成；外周组织的胆固醇逆向转运至肝脏后在细胞色素P450超家族(cytochrome P450 proteins，CYP)的作用下分解成胆汁酸或类固醇激素。胆固醇的分解代谢则受精脒/精胺-N1-乙酰基转移酶、Prospero相关同源蛋白1和Daxx等的严密调控；胆固醇逆向转运是防止动脉粥样硬化斑块和坏死中心形成的关键因素。肿瘤坏死因子α和红细胞很可能在巨噬细胞介导的胆固醇逆向转运中起着非常重要的作用。
关键词：
胆固醇；合成；分解；逆向转运；动脉粥样硬化
Progress in study on the regulation of cholesterol metabolism
CorrespondingAuthor: TUO Qinhui Email: qhtuo@yahoo.com.cn
DOI: 10.3978/j.issn.2095-6959.2014.01.012
Abstract
The metabolism of cholesterol, including biosynthesis, catabolism and reverse cholesterol transport, is closely related to a large number of diseases especially atherosclerosis. As a nuclear transcription factor, sterol regulatory element-binding proteins can accelerate the expression and activity of the key rate-limiting enzymes (such as 3-hydroxy-3-methylglutaryl-coenzyme A reductase),which is modulated by FoxO3 / Sirt6 complex, 3β-hydroxysterol ∆(24)-reductase and death domain associated protein (Daxx). The excessive cholesterol, antiported from peripheral tissue, was catabolized to bile acids and steroid hormones in liver, which is regulated by spermidine/spermine N1-acetyltransferase, Prospero-related homeodomain protein 1 and Daxx. Reverse cholesterol transport (RCT) plays a key role in the form of atherosclerotic plaque and necrotic core. It is likely that TNFα and red blood cells are involved in the RCT mediated by macrophages.