Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine
文献类型：期刊论文
| 作者 | Xie, C; Zhou, ZS; Li, N; Bian, Y; Wang, YJ; Wang, LJ; Li, BL; Song, BL |
| 刊名 | JOURNAL OF LIPID RESEARCH
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| 出版日期 | 2012 |
| 卷号 | 53期号:10页码:2092-2101 |
| 关键词 | Niemann-Pick C1 like1 cholesterol absorption endocytosis transport |
| 通讯作者 | Li, BL (reprint author), Chinese Acad Sci, State Key Lab Mol Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.,blli@sibs.ac.cn ; blsong@sibs.ac.cn |
| 英文摘要 | The multiple transmembrane protein Niemann-Pick C1 like1 (NPC1L1) is essential for intestinal cholesterol absorption. Ezetimibe binds to NPC1L1 and is a clinically used cholesterol absorption inhibitor. Recent studies in cultured cells have shown that NPC1L1 mediates cholesterol uptake through vesicular endocytosis that can be blocked by ezetimibe. However, how NPC1L1 and ezetimibe work in the small intestine is unknown. In this study, we found that NPC1L1 distributed in enterocytes of villi and transit-amplifying cells of crypts. Acyl-CoA cholesterol acyltransferase 2 (ACAT2), another important protein for cholesterol absorption by providing cholesteryl esters to chylomicrons, was mainly presented in the apical cytoplasm of enterocytes. NPC1L1 and ACAT2 were highly expressed in jejunum and ileum. ACAT1 presented in the Paneth cells of crypts and mesenchymal cells of villi. In the absence of cholesterol, NPC1L1 was localized on the brush border of enterocytes. Dietary cholesterol induced the internalization of NPC1L1 to the subapical layer beneath the brush border and became partially colocalized with the endosome marker Rab11. Ezetimibe blocked the internalization of NPC1L1 and cholesterol and caused their retention in the plasma membrane. This study demonstrates that NPC1L1 mediates cholesterol entering enterocytes through vesicular endocytosis and that ezetimibe blocks this step in vivo.-Xie, C., Z-S. Zhou, N. Li, Y. Bian, Y-J. Wang, L-J. Wang, B-L. Li, and B-L. Song. Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine. J. Lipid Res. 2012. 53: 2092-2101. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | DIET-INDUCED HYPERCHOLESTEROLEMIA ; ENDOCYTIC RECYCLING COMPARTMENT ; TRIGLYCERIDE TRANSFER PROTEIN ; PICK C1-LIKE 1 ; ACYL-COENZYME ; REGULATED TRANSLOCATION ; NONHUMAN-PRIMATES ; MOLECULAR-CLONING ; CELL-SURFACE ; HUMAN LIVER |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000308696600009 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/651]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Xie, C,Zhou, ZS,Li, N,et al. Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine[J]. JOURNAL OF LIPID RESEARCH,2012,53(10):2092-2101. |
| APA | Xie, C.,Zhou, ZS.,Li, N.,Bian, Y.,Wang, YJ.,...&Song, BL.(2012).Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine.JOURNAL OF LIPID RESEARCH,53(10),2092-2101. |
| MLA | Xie, C,et al."Ezetimibe blocks the internalization of NPC1L1 and cholesterol in mouse small intestine".JOURNAL OF LIPID RESEARCH 53.10(2012):2092-2101. |
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