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

J. Biol. Chem., Vol. 281, Issue 16, 11193-11204, April 21, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/16/11193    most recent M510261200v2 M510261200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted 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 Pagler, T. A. Articles by Stangl, H. Search for Related Content PubMed PubMed Citation Articles by Pagler, T. A. Articles by Stangl, H. Social Bookmarking                      What's this?

SR-BI-mediated High Density Lipoprotein (HDL) Endocytosis Leads to HDL Resecretion Facilitating Cholesterol Efflux^*

Tamara A. Pagler, Sebastian Rhode, Angelika Neuhofer, Hildegard Laggner, Wolfgang Strobl, Claudia Hinterndorfer, Ivo Volf^¶, Margit Pavelka^||, Erik R. M. Eckhardt^**, Deneys R. van der Westhuyzen^**1, Gerhard J. Schütz², and Herbert Stangl, Supported by the Austrian Science Foundation Grant P16362-B07³

From the Center for Physiology and Pathophysiology, Department of Medical Chemistry and ^¶Department of Physiology, Medical University of Vienna, Währingerstrasse 10, A-1090 Vienna, Austria, ^||Center for Anatomy and Cell Biology, Department of Cell Biology and Ultrastructure Research, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria, Institute of Biophysics, Johannes-Kepler-University Linz, Altenbergerstrasse 69, A-4040 Linz, Austria, and the ^**Departments of Internal Medicine and Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536-0200

The high density lipoprotein (HDL) receptor, scavenger receptor class B, type I (SR-BI), mediates selective cholesteryl ester uptake from lipoproteins into liver and steroidogenic tissues but also cholesterol efflux from macrophages to HDL. Recently, we demonstrated the uptake of HDL particles in SR-BI overexpressing Chinese hamster ovarian cells (ldlA7-SRBI) using ultrasensitive microscopy. In this study we show that this uptake of entire HDL particles is followed by resecretion. After uptake, HDL is localized in endocytic vesicles and organelles en route to the perinuclear area; many HDL-positive compartments were classified as multivesiculated and multilamellated organelles by electron microscopy. By using ¹²⁵I-labeled HDL, we found that 0.8% of the HDL added to the media is taken up by the ldlA7-SRBI cells within 1 h, and almost all HDL is finally resecreted. ¹²⁵I-Labeled low density lipoprotein showed a very similar association, uptake, and resecretion pattern in ldlA7-SRBI cells that do not express any low density lipoprotein receptor. Moreover, we demonstrate that the process of HDL cell association, uptake, and resecretion occurs in three physiologically relevant cell systems, the liver cell line HepG2, the adrenal cell line Y1BS1, and phorbol myristate acetate-differentiated THP-1 cells as a model for macrophages. Finally, we present evidence that HDL retroendocytosis represents one of the pathways for cholesterol efflux.

Received for publication, September 19, 2005 , and in revised form, February 16, 2006.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains videos 1-6.

¹ Supported by National Institutes of Health Grant HL63763.

² Supported by Austrian Science Foundation Grant P15053.

³ To whom correspondence should be addressed: Center for Physiology and Pathophysiology, Dept. of Medical Chemistry, Medical University of Vienna, Währingerstrasse 10, A-1090 Vienna, Austria. Tel.: 43-1-4277-60823; Fax: 43-1-4277-60881; E-mail: Herbert.Stangl{at}meduniwien.ac.at.

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

This article has been cited by other articles:

				C. Minahk, K.-W. Kim, R. Nelson, B. Trigatti, R. Lehner, and D. E. Vance Conversion of Low Density Lipoprotein-associated Phosphatidylcholine to Triacylglycerol by Primary Hepatocytes J. Biol. Chem., March 7, 2008; 283(10): 6449 - 6458. [Abstract] [Full Text] [PDF]

				T. A. Pagler, A. Neuhofer, H. Laggner, W. Strobl, and H. Stangl Cholesterol efflux via HDL resecretion occurs when cholesterol transport out of the lysosome is impaired J. Lipid Res., October 1, 2007; 48(10): 2141 - 2150. [Abstract] [Full Text] [PDF]

				T. J. F. Nieland, J. T. Shaw, F. A. Jaipuri, Z. Maliga, J. L. Duffner, A. N. Koehler, and M. Krieger Influence of HDL-cholesterol-elevating drugs on the in vitro activity of the HDL receptor SR-BI J. Lipid Res., August 1, 2007; 48(8): 1832 - 1845. [Abstract] [Full Text] [PDF]

				M. T. Catanese, R. Graziani, T. von Hahn, M. Moreau, T. Huby, G. Paonessa, C. Santini, A. Luzzago, C. M. Rice, R. Cortese, et al. High-Avidity Monoclonal Antibodies against the Human Scavenger Class B Type I Receptor Efficiently Block Hepatitis C Virus Infection in the Presence of High-Density Lipoprotein J. Virol., August 1, 2007; 81(15): 8063 - 8071. [Abstract] [Full Text] [PDF]

				Y. Zhang, A. M. Ahmed, N. McFarlane, C. Capone, D. R. Boreham, R. Truant, S. A. Igdoura, and B. L. Trigatti Regulation of SR-BI-mediated selective lipid uptake in Chinese hamster ovary-derived cells by protein kinase signaling pathways J. Lipid Res., February 1, 2007; 48(2): 405 - 416. [Abstract] [Full Text] [PDF]

				T. A. Pagler, S. Golsabahi, M. Doringer, S. Rhode, G. J. Schutz, M. Pavelka, C. Wadsack, M. Gauster, A. Lohninger, H. Laggner, et al. A Chinese Hamster Ovarian Cell Line Imports Cholesterol by High Density Lipoprotein Degradation J. Biol. Chem., December 15, 2006; 281(50): 38159 - 38171. [Abstract] [Full Text] [PDF]

				B. Sun, E. R. M. Eckhardt, S. Shetty, D. R. van der Westhuyzen, and N. R. Webb Quantitative analysis of SR-BI-dependent HDL retroendocytosis in hepatocytes and fibroblasts J. Lipid Res., August 1, 2006; 47(8): 1700 - 1713. [Abstract] [Full Text] [PDF]

				M. Dreux, T. Pietschmann, C. Granier, C. Voisset, S. Ricard-Blum, P.-E. Mangeot, Z. Keck, S. Foung, N. Vu-Dac, J. Dubuisson, et al. High Density Lipoprotein Inhibits Hepatitis C Virus-neutralizing Antibodies by Stimulating Cell Entry via Activation of the Scavenger Receptor BI J. Biol. Chem., July 7, 2006; 281(27): 18285 - 18295. [Abstract] [Full Text] [PDF]