Niemann-pick protein C1(NPC1) is a large integral membrane glycoprotein that resides in late endosomes,whereas niemann-pick protein C2(NPC2) is a small soluble protein found in the lumen of lysosomes.NPC1 protein is b...Niemann-pick protein C1(NPC1) is a large integral membrane glycoprotein that resides in late endosomes,whereas niemann-pick protein C2(NPC2) is a small soluble protein found in the lumen of lysosomes.NPC1 protein is believed to facilitate the transport of lipids,particularly cholesterol,from late endosomes/lysosomes to the Golgi apparatus,endoplasmic reticulum and plasma membrane.NPC2 primarily plays a role in the egress of cholesterol and glycolipids from lysosomes.Mutations in either NPC1 or NPC2 result in aberrant lipid transport from endocytic compartments,which results in lysosomal storage of a complex mixture of lipids,primarily cholesterol and glycosphingolipids.The NPC proteins regulate sterol homeostasis through production of LDL cholesterol-derived oxysterols.Oxysterols are endogenous ligands for the liver X receptors(LXRs),which can upregulate ATP binding cassette transporter A1(ABCA1) expression.ABCA1 may have antiatherogenic effects through the efflux of it-mediated cholesterol.Meanwhile,NPC1 heterozygote mutation confers substantial resistance to lesional necrosis and lesional macrophage apoptosis.Study of the NPC proteins will help us for further understanding of the mechanisms involved in atherogenesis.展开更多
尼曼-匹克C1型类似蛋白1(Niemann-Pick type C1 Like 1, NPC1L1)是一种跨膜蛋白,是外源性胆固醇吸收的重要因子,在体内胆固醇代谢过程中发挥十分重要的作用。NPC1L1与多种脂质转运体共同影响着胆固醇的代谢。细胞核受体主要通过作用于NP...尼曼-匹克C1型类似蛋白1(Niemann-Pick type C1 Like 1, NPC1L1)是一种跨膜蛋白,是外源性胆固醇吸收的重要因子,在体内胆固醇代谢过程中发挥十分重要的作用。NPC1L1与多种脂质转运体共同影响着胆固醇的代谢。细胞核受体主要通过作用于NPC1L1启动子区域调控NPC1L1的表达,进而影响胆固醇的吸收,但其影响胆固醇吸收的具体机制还没有完全清楚。NPC1L1的表达受多种因子的调节。多不饱和脂肪酸通过甾体调节原件结合蛋白2(sterol regulatory element binding protein 2, SREBP2)途径下调NPC1L1的表达。姜黄素及鞘氨醇等也参与NPC1L1表达的调节。降脂药物依泽替米贝(ezetimibe)可通过降低NPC1L1的表达减少胆固醇的吸收从而降低血浆胆固醇的水平,同时对其它脂类代谢病也有一定的作用。本文对NPC1L1在结构、功能和调节方面的研究进展做一综述。展开更多
文摘目的观察肠道胆固醇吸收抑制剂依泽替米贝(ezetimibe)对RAW264.7细胞源性荷脂细胞脂质蓄积的影响并对其机制进行初步探讨。方法采用油红O染色、高效液相色谱法检测细胞内脂滴数量和细胞内脂质含量,Western blot对NPC1L1(Niemann-Pick type C1Like-1)进行定性和半定量检测。结果RAW264.7细胞中有NPC1L1蛋白表达。不同浓度(0、0.003、0.01和0.03mol.L-1)依泽替米贝预先孵育RAW264.7细胞24h或最佳浓度(0.03mol.L-1)预先孵育不同时间(0、6、12和24h)后,换50mg.L-1oxLDL继续孵育24h,结果显示不同浓度ezetimibe预先孵育后,细胞内脂滴数量与面积随着浓度的增加而逐渐减少;Ezetimibe预先孵育可减少细胞内脂质蓄积,并呈浓度和时间依赖性。其中0.03mol.L-1ezetimibe预先孵育24h组作用最明显,CE百分比较oxLDL单独孵育组减少了约47%±0.1%。结论小鼠源性巨噬细胞RAW264.7中存在NPC1L1蛋白表达;依泽替米贝能够减少RAW264.7细胞中NPC1L1蛋白表达;依泽替米贝抑制RAW264.7细胞中脂质蓄积。
文摘Niemann-pick protein C1(NPC1) is a large integral membrane glycoprotein that resides in late endosomes,whereas niemann-pick protein C2(NPC2) is a small soluble protein found in the lumen of lysosomes.NPC1 protein is believed to facilitate the transport of lipids,particularly cholesterol,from late endosomes/lysosomes to the Golgi apparatus,endoplasmic reticulum and plasma membrane.NPC2 primarily plays a role in the egress of cholesterol and glycolipids from lysosomes.Mutations in either NPC1 or NPC2 result in aberrant lipid transport from endocytic compartments,which results in lysosomal storage of a complex mixture of lipids,primarily cholesterol and glycosphingolipids.The NPC proteins regulate sterol homeostasis through production of LDL cholesterol-derived oxysterols.Oxysterols are endogenous ligands for the liver X receptors(LXRs),which can upregulate ATP binding cassette transporter A1(ABCA1) expression.ABCA1 may have antiatherogenic effects through the efflux of it-mediated cholesterol.Meanwhile,NPC1 heterozygote mutation confers substantial resistance to lesional necrosis and lesional macrophage apoptosis.Study of the NPC proteins will help us for further understanding of the mechanisms involved in atherogenesis.
基金supported by the National Natural Science Foundation of China (No.81071416)
文摘尼曼-匹克C1型类似蛋白1(Niemann-Pick type C1 Like 1, NPC1L1)是一种跨膜蛋白,是外源性胆固醇吸收的重要因子,在体内胆固醇代谢过程中发挥十分重要的作用。NPC1L1与多种脂质转运体共同影响着胆固醇的代谢。细胞核受体主要通过作用于NPC1L1启动子区域调控NPC1L1的表达,进而影响胆固醇的吸收,但其影响胆固醇吸收的具体机制还没有完全清楚。NPC1L1的表达受多种因子的调节。多不饱和脂肪酸通过甾体调节原件结合蛋白2(sterol regulatory element binding protein 2, SREBP2)途径下调NPC1L1的表达。姜黄素及鞘氨醇等也参与NPC1L1表达的调节。降脂药物依泽替米贝(ezetimibe)可通过降低NPC1L1的表达减少胆固醇的吸收从而降低血浆胆固醇的水平,同时对其它脂类代谢病也有一定的作用。本文对NPC1L1在结构、功能和调节方面的研究进展做一综述。
基金supported by the National Natural Science Foundation of China(No.81400936)the Joint Foundation for Fostering Talents of NSFC-Henan ProvinceChina(No.U1304808)
