HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M400179-JLR200v1 45/9/1758    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhou, J. Articles by Mallampalli, R. K. Search for Related Content PubMed PubMed Citation Articles by Zhou, J. Articles by Mallampalli, R. K. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 45, 1758-1767, September 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Upregulation of surfactant synthesis triggers ABCA1-mediated basolateral phospholipid efflux

Jiming Zhou^*, Yong You^*, Alan J. Ryan^*, and Rama K. Mallampalli^1,,

^* Departments of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242
Department of Veterans Affairs Medical Center, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242

¹ To whom correspondence should be addressed. e-mail: rama-mallampalli{at}uiowa.edu

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 (CCT), 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 CCT in lung epithelial cell lines increased rates of PC synthesis and cellular DSPC mass without altering total cellular PC content. Overexpression of CCT 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.

Abbreviations: CCT, CTP:phosphocholine cytidylyltransferase; CDP-choline, cytidine diphosphocholine; DOPC, 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphocholine; DR-4, direct repeat separated by four nucleotides; DPPC, dipalmitoyl phosphatidylcholine; DSPC, disaturated phosphatidylcholine; ECL, enhanced chemiluminescence; GPC, glycerophosphocholine; 22HC, 22-hydroxycholesterol; LXR, liver X receptor; PC, phosphatidylcholine; POPC, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine; RA, 9-cis retinoic acid; RXR, retinoid X receptor

Supplementary key words CTP:phosphocholine cytidylyltransferase • phosphatidylcholine • ATP binding cassette transporter 1 • human lung adenocarcinoma cell line • overexpression

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. R. Bates, J.-Q. Tao, K. J. Yu, Z. Borok, E. D. Crandall, H. L. Collins, and G. H. Rothblat Expression and Biological Activity of ABCA1 in Alveolar Epithelial Cells Am. J. Respir. Cell Mol. Biol., March 1, 2008; 38(3): 283 - 292. [Abstract] [Full Text] [PDF]

				R. L. Jacobs, S. Lingrell, Y. Zhao, G. A. Francis, and D. E. Vance Hepatic CTP:Phosphocholine Cytidylyltransferase-{alpha} Is a Critical Predictor of Plasma High Density Lipoprotein and Very Low Density Lipoprotein J. Biol. Chem., January 25, 2008; 283(4): 2147 - 2155. [Abstract] [Full Text] [PDF]

				A. V. Andreeva, M. A. Kutuzov, and T. A. Voyno-Yasenetskaya Regulation of surfactant secretion in alveolar type II cells Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L259 - L271. [Abstract] [Full Text] [PDF]

				A. Baldan, P. Tarr, C. S. Vales, J. Frank, T. K. Shimotake, S. Hawgood, and P. A. Edwards Deletion of the Transmembrane Transporter ABCG1 Results in Progressive Pulmonary Lipidosis J. Biol. Chem., September 29, 2006; 281(39): 29401 - 29410. [Abstract] [Full Text] [PDF]

				F. Brasch, S. Schimanski, C. Muhlfeld, S. Barlage, T. Langmann, C. Aslanidis, A. Boettcher, A. Dada, H. Schroten, E. Mildenberger, et al. Alteration of the Pulmonary Surfactant System in Full-Term Infants with Hereditary ABCA3 Deficiency Am. J. Respir. Crit. Care Med., September 1, 2006; 174(5): 571 - 580. [Abstract] [Full Text] [PDF]

				J. F. Oram and J. W. Heinecke ATP-Binding Cassette Transporter A1: A Cell Cholesterol Exporter That Protects Against Cardiovascular Disease Physiol Rev, October 1, 2005; 85(4): 1343 - 1372. [Abstract] [Full Text] [PDF]

				S. Jackowski and P. Fagone CTP:Phosphocholine Cytidylyltransferase: Paving the Way from Gene to Membrane J. Biol. Chem., January 14, 2005; 280(2): 853 - 856. [Full Text] [PDF]