氨肽酶N (CD13)是一种胆固醇吸收抑制剂的分子目标ezetimibe的肠上皮细胞刷状缘膜。
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克雷默W, Girbig F, Corsiero D, Pfenninger,弗里克W, Jahne G,大黄酸M, Wendler W, Lottspeich F, Hochleitner EO,施密茨Orso E, G
氨肽酶N (CD13)是一种胆固醇吸收抑制剂的分子目标ezetimibe的肠上皮细胞刷状缘膜。
J生物化学杂志。2005年1月14日,280 (2):1306 - 20。Epub 2004年10月19日。
- PubMed ID
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15494415 (在PubMed]
- 文摘
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肠内胆固醇的吸收是一个重要的监管机构的血清胆固醇水平。Ezetimibe是特定的肠道内胆固醇吸收抑制剂最近引入医疗实践;然而,其作用机理还不清楚。Ezetimibe既不影响释放胆固醇在肠道内腔和混合胶束的胆固醇转移到肠上皮细胞刷状缘膜。与membrane-impermeable Ezetimibe类似我们可以证明绑定的胆固醇吸收抑制剂小肠肠上皮细胞刷状缘膜的肠道流明是充分的抑制胆固醇的吸收。145 kda积分膜蛋白被确认为胆固醇吸收抑制剂的分子目标的肠上皮细胞刷状缘膜通过光亲和标记photoreactive Ezetimibe类似物(克莱默,W。Glombik, H。诗,S。,豪雅,H。谢弗,h·L。Wendler, W。Corsiero D。Girbig F。,,。维兰德提出c(2000) 2月。487年,293 - 297)。145 kda Ezetimibe-binding蛋白质是由三个不同的纯化方法和测序透露其身份与膜结合胞外酶氨基肽酶N(丙氨酰氨肽酶; EC 3.4.11.2; APN; leukemia antigen CD13). The enzymatic activity of APN was not influenced by Ezetimibe (analogues). The uptake of cholesterol delivered by mixed micelles by confluent CaCo-2 cells was partially inhibited by Ezetimibe and nonabsorbable Ezetimibe analogues. Preincubation of confluent CaCo-2 cells with Ezetimibe led to a strong decrease of fluorescent APN staining with a monoclonal antibody in the plasma membrane. Independent on its enzymatic activity, aminopeptidase N is involved in endocytotic processes like the uptake of viruses. Our findings suggest that binding of Ezetimibe to APN from the lumen of the small intestine blocks endocytosis of cholesterol-rich membrane microdomains, thereby limiting intestinal cholesterol absorption.