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

J. Biol. Chem., Vol. 280, Issue 8, 6766-6779, February 25, 2005

This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 280/8/6766    most recent M413238200v4 M413238200v1 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 Wüstner, D. Search for Related Content PubMed PubMed Citation Articles by Wüstner, D. Social Bookmarking                      What's this?

Mathematical Analysis of Hepatic High Density Lipoprotein Transport Based on Quantitative Imaging Data^*

Daniel Wüstner

From the Theoretical Biophysics Group, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13125 Berlin, Germany

Hepatocytes internalize high density lipoprotein (HDL) at the basolateral membrane. Most HDL is recycled while some is shuttled to the canalicular membrane by transcytosis. Here, transport of HDL was analyzed by mathematical modeling based on measurements in polarized hepatic HepG2 cells. Recycling of HDL from basolateral sorting endosomes was modeled by applying the rapid equilibrium approach. Analytical expressions were derived, which describe in one model the transport of HDL to the subapical compartment/apical recycling compartment, the biliary canaliculus (BC), and to late endosomes and lysosomes (LE/LYS). Apical endocytosis of HDL predicted by the model was confirmed for rhodamine-dextran and fluorescent asialoorosomucoid, markers for LE/LYS in living HepG2 cells. Budding of endocytic vesicles from the BC was directly observed by time lapse imaging of a fluorescent lipid probe. Based on fitted kinetic parameters and their covariance matrix a Monte Carlo simulation of HDL transport in hepatocytes was performed. The model was used to quantitatively assess release of HDL-associated free cholesterol by scavenger receptor BI. It is shown that only 6% of HDL-associated sterol reaches the BC as a constituent of the HDL particles, whereas the remaining sterol is rapidly released from HDL and shuttled to the BC by non-vesicular transport.

Received for publication, November 23, 2004

^* This work was supported by a postdoctoral fellowship of the Max-Delbrück Center. 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 supplementary data.

To whom correspondence should be addressed: Theoretical Biophysics Group, Max-Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, D-13125 Berlin, Germany. Tel.: 49-30-9406-3713; Fax: 49-30-9406-2548; E-mail: da.wuestner{at}mdc-berlin.de.

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

This article has been cited by other articles:

				L. Rohrer, P. M. Ohnsorg, M. Lehner, F. Landolt, F. Rinninger, and A. von Eckardstein High-Density Lipoprotein Transport Through Aortic Endothelial Cells Involves Scavenger Receptor BI and ATP-Binding Cassette Transporter G1 Circ. Res., May 22, 2009; 104(10): 1142 - 1150. [Abstract] [Full Text] [PDF]

				N. H. Petersen, N. J. Faergeman, L. Yu, and D. Wustner Kinetic imaging of NPC1L1 and sterol trafficking between plasma membrane and recycling endosomes in hepatoma cells J. Lipid Res., September 1, 2008; 49(9): 2023 - 2037. [Abstract] [Full Text] [PDF]

				C. J. Harder, A. Meng, P. Rippstein, H. M. McBride, and R. McPherson SR-BI Undergoes Cholesterol-stimulated Transcytosis to the Bile Canaliculus in Polarized WIF-B Cells J. Biol. Chem., January 12, 2007; 282(2): 1445 - 1455. [Abstract] [Full Text] [PDF]

				D. Wustner Plasma Membrane Sterol Distribution Resembles the Surface Topography of Living Cells Mol. Biol. Cell, January 1, 2007; 18(1): 211 - 228. [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]

				E. R. M. Eckhardt, L. Cai, S. Shetty, Z. Zhao, A. Szanto, N. R. Webb, and D. R. Van der Westhuyzen High Density Lipoprotein Endocytosis by Scavenger Receptor SR-BII Is Clathrin-dependent and Requires a Carboxyl-terminal Dileucine Motif J. Biol. Chem., February 17, 2006; 281(7): 4348 - 4353. [Abstract] [Full Text] [PDF]