ABCA1 is essential for efficient basolateral cholesterol efflux during the absorption of dietary cholesterol in chickens
ABCA1 is essential for efficient basolateral cholesterol efflux during the absorption of dietary cholesterol in chickens
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DOI：
10.1074/jbc.m212377200
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发表时间：
2003-04-11
影响因子：
4.8
通讯作者：
Attie, AD
中科院分区：
文献类型：
--
作者：
Mulligan, JD;Flowers, MT;Attie, AD
ATP结合盒转运蛋白A1（ABCA 1）参与胆固醇从细胞中流出。目前尚不清楚ABCA1是否具有将胆固醇流出肠基底膜或顶膜的功能。我们用过。ABCA 1功能障碍的鸡模型，威斯康星州低α突变（WHAM）鸡，来解决这个问题。经口灌胃放射性胆固醇后，WHAM鸡血液中出现的百分比降低了79%沿着高密度脂蛋白中示踪剂的量降低了97%。相反，从管腔吸收到肠中的放射性胆固醇的百分比不受ABCA 1突变的影响。肝X受体（LXR）激动剂已被推断通过激活ABCA 1表达来减少胆固醇吸收。然而，LXR激动剂T0901317在野生型和WHAM鸡中同样降低胆固醇吸收，表明LXR激活对胆固醇吸收的影响不依赖于ABCA 1。ABCA 1突变导致放射性胆固醇酯在WHAM鸡的肠和肝中积累（分别为5.0倍和4.4倍），而胆汁脂质浓度未被WHAM突变改变。总之，ABCA 1调节胆固醇从肠和肝中的基底膜而不是顶膜的流出。
The ATP-binding cassette transporter A1 (ABCA1) participates in the efflux of cholesterol from cells. It remains unclear whether ABCA1 functions to efflux cholesterol across the basolateral or apical membrane of the intestine. We used. a chicken model of ABCA1 dysfunction, the Wisconsin hypoalpha mutant (WHAM) chicken, to address this issue. After an oral gavage of radioactive cholesterol, the percentage appearing in the bloodstream was reduced by 79% in the WHAM chicken along with a 97% reduction in the amount of tracer in high density lipoprotein. In contrast, the percentage of radioactive cholesterol absorbed from the lumen into the intestine was not affected by the ABCA1 mutation. Liver X receptor (LXR) agonists have been inferred to decrease cholesterol absorption through activation of ABCA1 expression. However, the LXR agonist T0901317 decreased cholesterol absorption equally in both wild type and WHAM chickens, indicating that the effect of LXR activation on cholesterol absorption is independent of ABCA1 The ABCA1 mutation resulted in accumulation of radioactive cholesterol ester in the intestine and the liver of the WHAM chicken (5.0- and 4.4-fold, respectively), whereas biliary lipid concentrations were unaltered by the WHAM mutation. In summary, ABCA1 regulates the efflux of cholesterol from the basolateral but not apical membrane in the intestine and the liver.