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Regulation of intestinal cholesterol absorption.
Annual Review of Physiology ( IF 15.7 ) Pub Date : 2006-09-28 , DOI: 10.1146/annurev.physiol.69.031905.160725
David Q-H Wang 1
Affiliation  

The identification of defective structures in the ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 in patients with sitosterolemia suggests that these two proteins are an apical sterol export pump promoting active efflux of cholesterol and plant sterols from enterocytes back into the intestinal lumen for excretion. The newly identified Niemann-Pick C1-like 1 (NPC1L1) protein is also expressed at the apical membrane of enterocytes and plays a crucial role in the ezetimibe-sensitive cholesterol absorption pathway. These findings indicate that cholesterol absorption is a multistep process that is regulated by multiple genes at the enterocyte level and that the efficiency of cholesterol absorption may be determined by the net effect between influx and efflux of intraluminal cholesterol molecules crossing the brush border membrane of the enterocyte. Combination therapy using cholesterol absorption (NPC1L1) inhibitor (ezetimibe) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) provides a powerful novel strategy for the prevention and treatment of hypercholesterolemia.

中文翻译:

调节肠道胆固醇的吸收。

对谷固醇血症患者中的ATP结合盒(ABC)转运蛋白ABCG5和ABCG8中缺陷结构的鉴定表明,这两种蛋白是一种顶端甾醇输出泵,可促进胆固醇和植物甾醇从肠细胞向肠腔的有效外排,从而排泄到肠腔。 。新鉴定的Niemann-Pick C1样1(NPC1L1)蛋白也在肠上皮细胞的顶膜表达,并且在依泽替米贝敏感的胆固醇吸收途径中起着至关重要的作用。这些发现表明,胆固醇的吸收是一个多步骤过程,在肠上皮细胞水平上由多个基因调节,胆固醇的吸收效率可以通过腔内胆固醇分子穿过肠上皮刷状缘膜的流入和流出之间的净效应来确定。 。使用胆固醇吸收(NPC1L1)抑制剂(ezetimibe)和3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂(他汀类药物)的联合疗法为预防和治疗高胆固醇血症提供了强有力的新策略。
更新日期:2019-11-01
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