Lipoproteins are protein-lipid macromolecular assemblies which are used to transport lipids in circulation and are key targets in cardiovascular disease （CVD）. The highly dynamic lipoprotein molecules are capable of...Lipoproteins are protein-lipid macromolecular assemblies which are used to transport lipids in circulation and are key targets in cardiovascular disease （CVD）. The highly dynamic lipoprotein molecules are capable of adopting an array of conformations that is crucial to lipid transport along the cholesterol transport pathway, among which high-density lipopro- tein （HDL） and low-density lipoprotein （LDL） are major players in plasma cholesterol metabolism. For a more detailed illustration of cholesterol transport process, as well as the development of therapies to prevent CVD, here we review the functional mechanism and structural basis of lipoproteins in cholesterol transport, as well as their structural dynamics in the plasma lipoprotein （HDL and LDL） elevations, in order to obtain better quantitative understandings on structure-function relationship of lipoproteins. Finally, we also provide an approach for further research on the lipoprotein in cholesterol transport.展开更多
胆固醇是生命活动必不可少的脂类物质,胆固醇浓度过高或者过低均对人体有害。但由体内胆固醇水平过高引起高胆固醇血症,是导致动脉粥样硬化、脑中风和冠心病的重要危险因素之一。人体内胆固醇有两种来源:以乙酰辅酶A为原料从头合成,或...胆固醇是生命活动必不可少的脂类物质,胆固醇浓度过高或者过低均对人体有害。但由体内胆固醇水平过高引起高胆固醇血症,是导致动脉粥样硬化、脑中风和冠心病的重要危险因素之一。人体内胆固醇有两种来源:以乙酰辅酶A为原料从头合成,或者通过小肠从食物中吸收。现今,过量的胆固醇摄取是引起高胆固醇血症的重要原因。胆固醇在小肠中的吸收是一个复杂的、多步骤的连续分解、转运以及重新酯化的过程。其中Niemann-Pick C1 Like 1(NPC1L1)蛋白介导肠道中胆固醇进入血液,是胆固醇吸收的限速步骤。胆固醇转运蛋白(CETP)介导血浆脂蛋白之间胆固醇的转运,在胆固醇逆转运过程中发挥关键作用。研究表明抑制外源性胆固醇的吸收和转运能够较好地降低血液中胆固醇的浓度,有效预防和降低心血管疾病的发生。本文重点总结了胆固醇代谢紊乱的相关疾病和肠道胆固醇吸收的分子途径、调控机制、药物研发现状。展开更多
目的:探讨吡格列酮对THP-1源性巨噬细胞ATP结合盒转运蛋白A1(ABCA1)、ATP结合盒转运蛋白G1(ABCG1)及B族Ⅰ型清道夫受体(SR-BⅠ)表达的影响及可能作用机制。方法:Real time PCR及Western-blot检测不同浓度吡格列酮(1,10,20,30μmol/L)作...目的:探讨吡格列酮对THP-1源性巨噬细胞ATP结合盒转运蛋白A1(ABCA1)、ATP结合盒转运蛋白G1(ABCG1)及B族Ⅰ型清道夫受体(SR-BⅠ)表达的影响及可能作用机制。方法:Real time PCR及Western-blot检测不同浓度吡格列酮(1,10,20,30μmol/L)作用24h,THP-1源性巨噬细胞ABCA1,ABCG1及SR-BⅠmRNA和蛋白的表达。使用过氧化物酶体增殖物激活型受体γ(PPARγ)特异性拮抗剂GW9662(2μmol/L)阻断吡格列酮(10μmol/L),24h后检测THP-1源性巨噬细胞ABCA1,ABCG1及SR-BⅠmRNA和蛋白的表达。结果:吡格列酮可浓度依赖性增高24hTHP-1源性巨噬细胞ABCA1,ABCG1及SR-BⅠmRNA和蛋白的表达,GW9662可显著抑制吡格列酮诱导的THP-1源性巨噬细胞ABCA1,ABCG1及SR-BⅠmRNA和蛋白表达的增高(P<0.05)。结论:吡格列酮激动PPARγ上调THP-1源性巨噬细胞胆固醇流出调节蛋白ABCA1,ABCG1及SR-BⅠ基因的表达。展开更多
基金Project supported by the National Natural Science Foundation of China(Grant Nos.11504287 and 11774279)
文摘Lipoproteins are protein-lipid macromolecular assemblies which are used to transport lipids in circulation and are key targets in cardiovascular disease （CVD）. The highly dynamic lipoprotein molecules are capable of adopting an array of conformations that is crucial to lipid transport along the cholesterol transport pathway, among which high-density lipopro- tein （HDL） and low-density lipoprotein （LDL） are major players in plasma cholesterol metabolism. For a more detailed illustration of cholesterol transport process, as well as the development of therapies to prevent CVD, here we review the functional mechanism and structural basis of lipoproteins in cholesterol transport, as well as their structural dynamics in the plasma lipoprotein （HDL and LDL） elevations, in order to obtain better quantitative understandings on structure-function relationship of lipoproteins. Finally, we also provide an approach for further research on the lipoprotein in cholesterol transport.
文摘胆固醇是生命活动必不可少的脂类物质,胆固醇浓度过高或者过低均对人体有害。但由体内胆固醇水平过高引起高胆固醇血症,是导致动脉粥样硬化、脑中风和冠心病的重要危险因素之一。人体内胆固醇有两种来源:以乙酰辅酶A为原料从头合成,或者通过小肠从食物中吸收。现今,过量的胆固醇摄取是引起高胆固醇血症的重要原因。胆固醇在小肠中的吸收是一个复杂的、多步骤的连续分解、转运以及重新酯化的过程。其中Niemann-Pick C1 Like 1(NPC1L1)蛋白介导肠道中胆固醇进入血液,是胆固醇吸收的限速步骤。胆固醇转运蛋白(CETP)介导血浆脂蛋白之间胆固醇的转运,在胆固醇逆转运过程中发挥关键作用。研究表明抑制外源性胆固醇的吸收和转运能够较好地降低血液中胆固醇的浓度,有效预防和降低心血管疾病的发生。本文重点总结了胆固醇代谢紊乱的相关疾病和肠道胆固醇吸收的分子途径、调控机制、药物研发现状。
文摘目的:探讨吡格列酮对THP-1源性巨噬细胞ATP结合盒转运蛋白A1(ABCA1)、ATP结合盒转运蛋白G1(ABCG1)及B族Ⅰ型清道夫受体(SR-BⅠ)表达的影响及可能作用机制。方法:Real time PCR及Western-blot检测不同浓度吡格列酮(1,10,20,30μmol/L)作用24h,THP-1源性巨噬细胞ABCA1,ABCG1及SR-BⅠmRNA和蛋白的表达。使用过氧化物酶体增殖物激活型受体γ(PPARγ)特异性拮抗剂GW9662(2μmol/L)阻断吡格列酮(10μmol/L),24h后检测THP-1源性巨噬细胞ABCA1,ABCG1及SR-BⅠmRNA和蛋白的表达。结果:吡格列酮可浓度依赖性增高24hTHP-1源性巨噬细胞ABCA1,ABCG1及SR-BⅠmRNA和蛋白的表达,GW9662可显著抑制吡格列酮诱导的THP-1源性巨噬细胞ABCA1,ABCG1及SR-BⅠmRNA和蛋白表达的增高(P<0.05)。结论:吡格列酮激动PPARγ上调THP-1源性巨噬细胞胆固醇流出调节蛋白ABCA1,ABCG1及SR-BⅠ基因的表达。
