Multiple, independently regulated pathways of cholesterol transport across the intestinal epithelial cells
Multiple, independently regulated pathways of cholesterol transport across the intestinal epithelial cells
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DOI：
10.1074/jbc.m301177200
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发表时间：
2003-08-22
影响因子：
4.8
通讯作者：
Hussain, MM
中科院分区：
文献类型：
--
作者：
Iqbal, J;Anwar, K;Hussain, MM
本研究为肠细胞吸收胆固醇的机制提供了新的认识。与一般看法相反，我们的数据表明，新吸收的胆固醇既不能立即与载脂蛋白一起分泌，也不能作为乳糜微粒的一部分专门分泌。根据我们的数据，肠细胞的胆固醇转运可以大致分为两种独立调节的途径，载脂蛋白依赖性和非依赖性。载脂蛋白依赖途径的胆固醇分泌由油酸诱导，由微粒体甘油三酯转移蛋白抑制剂抑制，并且仅在较大的载脂蛋白中发生。载脂蛋白非依赖性途径不需要微粒体甘油三酯转移蛋白，并涉及由ABCA1介导的外排、高密度脂蛋白组装和可能的其他未知机制。至少有两种不同的胆固醇代谢池。新吸收和预吸收的胆固醇分别通过载脂蛋白非依赖性和载脂蛋白依赖性途径优先分泌。与分泌的区隔化相反，这两个代谢池同样可用于细胞酯化。酯化胆固醇主要通过载脂蛋白依赖途径分泌，而这两种途径都参与游离胆固醇的分泌。因此，肠细胞通过几种独立调节的途径运输外源性胆固醇，这提高了靶向载脂蛋白非依赖性途径可能导致选择性抑制胆固醇运输而不影响甘油三酯运输的可能性。
The present study provides a new understanding about the mechanisms involved in cholesterol absorption by the intestinal cells. Contrary to general belief, our data show that newly absorbed cholesterol is neither immediately available for secretion with apoB lipoproteins nor exclusively secreted as part of chylomicrons. Based on our data, cholesterol transport by enterocytes can be broadly classified into two independently modulated, apoB-dependent and -independent, pathways. Cholesterol secretion by the apoB-dependent pathway is induced by oleic acid, is repressed by microsomal triglyceride transfer protein inhibitors, and occurs only with larger apoB-containing lipoproteins. ApoB-independent pathways do not require microsomal triglyceride transfer protein and involve efflux mediated by ABCA1, high density lipoprotein assembly, and possibly other unknown mechanisms. There are at least two different metabolic pools of cholesterol. The newly absorbed and pre-absorbed cholesterol are preferentially secreted via apoB-independent and apoB-dependent pathways, respectively. In contrast to compartmentalization for secretion, these two metabolic pools are equally accessible for cellular esterification. The esterified cholesterol is mainly secreted by the apoB-dependent pathway, whereas both the pathways are involved in the secretion of free cholesterol. Thus, enterocytes transport exogenous cholesterol by several independently regulated pathways raising the possibility that targeting of apoB-independent pathways may result in selective inhibition of cholesterol transport without affecting triglyceride transport.