NPC1L1-mediated cholesterol uptake

Dietary cholesterol is taken up into enterocytes from the gut lumen in a reaction mediated by plasma membrane-associated NPC1L1 protein. Detailed studies in Maden-Darby canine kidney cells, both mediated by endogenous (canine) NPC1L1 and by overexpressed human protein, indicate a major role for NPC1L1 in the uptake of extracellular cholesterol. These studies have also shown that ezetimibe binds both human and canine proteins and renders them incapable of mediating cholesterol uptake. The molecular mechanisms of cholesterol transport and ezetimibe inhibition, however, remain unclear (Weinglass et al. 2008).

膳食胆固醇通过肠道绒毛细胞对肠腔内物质的摄取作用，这一作用由与质膜关联的NPC1L1蛋白介导。在Maden-Darby犬肾细胞中进行的详细研究，无论是内源性的（犬）NPC1L1介导，还是通过过表达的人源蛋白，均表明NPC1L1在细胞外胆固醇摄取过程中发挥着重要作用。这些研究亦表明，依泽替米对人类和犬类蛋白具有结合作用，使其无法介导胆固醇的摄取。然而，胆固醇转运的分子机制及依泽替米的抑制作用仍不明确（Weinglass等，2008）。