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标题：Upregulation of surfactant synthesis triggers ABCA1-mediated basolateral phospholipid efflux
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作者：Jiming Zhou ; Yong You ; Alan J. Ryan 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2004
卷号：45
期号：9
页码：1758-1767
DOI：10.1194/jlr.M400179-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Alveolar type II lung epithelia produce surfactant, an essential surface-active material highly enriched with disaturated phosphatidylcholine (DSPC), which requires a key regulatory enzyme, CTP:phosphocholine cytidylyltransferase α (CCTα), for its synthesis before its export apically into the alveolus. In this study, we examined whether surfactant phosphatidylcholine (PC) synthesis and export are physiologically linked. Stable overexpression of CCTα in lung epithelial cell lines increased rates of PC synthesis and cellular DSPC mass without altering total cellular PC content. Overexpression of CCTα was associated with i ) increased basolateral, rather than apical, PC export catalyzed by ABCA1; ii ) basolateral export of significant levels of unsaturated (nonsurfactant) PC; and iii ) transcriptional activation of the ABCA1 gene via a liver X receptor/retinoic acid receptor-independent pathway. Cells exposed to PC vesicles exhibited a dose-dependent increase in ABCA1 transcriptional activity. These data provide the first evidence that surfactant PC synthesis is linked to its export via a basolateral lipid efflux pathway. This pathway is mediated, in part, by a phospholipid sensor, ABCA1, that appears to partake in the autoregulation of both cellular content and composition of PC, thereby providing a potentially novel exit route for a newly synthesized pool of PC distinct from surfactant.