Identification and characterization of rodent ABCA1 in isolated type II pneumocytes
Identification and characterization of rodent ABCA1 in isolated type II pneumocytes
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DOI：
10.1152/ajplung.00077.2003
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发表时间：
2003-10-01
影响因子：
4.9
通讯作者：
Bates, SR
中科院分区：
文献类型：
--
作者：
Bortnick, AE;Favari, E;Bates, SR
atp结合盒转运蛋白A1 （ABCA1）促进胆固醇和磷脂从细胞向无脂血清载脂蛋白的转移。5 μ M 9-顺式维甲酸（9cRA）和6.2 μ M 22-羟基胆固醇（22-OH）对鼠ⅱ型细胞原代培养ABCA1 mRNA和蛋白表达上调敏感。ABCA1蛋白水平的增加是时间依赖性的，在暴露于9cRA + 22-OH 16 h后达到最大。在转化的肺源细胞系WI38/VA13、A549和NIH-H441细胞中也发现了可诱导的ABCA1。9cRA + 22-OH刺激大鼠II型细胞中的ABCA1，可使放射性磷脂或胆固醇从肺细胞向载脂蛋白AI （apo AI）的外排分别增强4倍或5倍，而cAMP （0.3 mM）则没有影响。ABCA1介导的脂质外排不依赖于表面活性剂的分泌途径，因为ABCA1的上调导致分泌剂刺激的表面活性剂磷脂释放减少。这些研究证实了肺ⅱ型细胞中功能性ABCA1的存在。
ATP-binding cassette transporter A1 (ABCA1) promotes transfer of cholesterol and phospholipid from cells to lipid-free serum apolipoproteins. ABCA1 mRNA and protein expression in primary cultures of rodent type II cells was sensitive to upregulation with 5 muM 9-cis-retinoic acid (9cRA) and 6.2 mu M 22-hydroxycholesterol (22-OH). The increase in ABCA1 protein levels was time dependent and was maximal after 16 h of exposure to 9cRA + 22-OH. Inducible ABCA1 was also found in transformed cell lines of lung origin: WI38/VA13, A549, and NIH-H441 cells. Stimulation of ABCA1 in rat type II cells by 9cRA + 22-OH resulted in a four- or fivefold enhancement of efflux of radioactive phospholipid or cholesterol, respectively, from the pneumocytes to apolipoprotein AI (apo AI), whereas cAMP (0.3 mM) had no effect. ABCA1-mediated lipid efflux to apo AI was independent of the surfactant secretion pathway, inasmuch as upregulation of ABCA1 resulted in a reduction of secretagogue-stimulated surfactant phospholipid release. These studies demonstrate the presence of functional ABCA1 in type II cells from the lung.