|
|
||||||||
Correspondence to: Theodore Mazzone, at Rush Medical Center, 1653 West Congress Pkwy., Chicago, IL 60612., tmazzone{at}rush.edu (E-mail)
Macrophages express a number of proteins involved in sterol efflux pathways, including apolipoprotein E (apoE) and scavenger receptor class B type I (SR-BI). We have investigated a potential interaction between these two sterol efflux pathways in modulating overall macrophage sterol flux. We utilized an experimental system in which we increased expression of each of these proteins to a high physiologic range in order to perform our evaluation. We show that in apoE-expressing cells, a 4-fold increase in SR-BI expression leads to reduction of sterol and phospholipid efflux. SR-BI-mediated reduction in sterol efflux was only observed in cells that expressed endogenous apoE. In J774 cells that did not express apoE, a similar increase in SR-BI level led to increased sterol efflux. The divergent response of sterol efflux after increased SR-BI was maintained in the presence of a number of structurally diverse extracellular sterol acceptors. Increased SR-BI expression also enhanced sterol efflux to exogenously added apoE. Investigation of a potential mechanism for reduced efflux in apoE-expressing cells indicated that SR-BI expression reduced macrophage apoE by accelerating the degradation of newly synthesized apoE. This led to decreased secretion of apoE and reduced the fraction of apoE sequestered on the cell surface.
Thus, enhanced SR-BI expression in macrophages can reduce the cellular level and secretion of apoE by accelerating degradation of the newly synthesized protein. This reduction of endogenous apoE is accompanied by reduced sterol efflux from macrophages. Huang, Z. H., and T. Mazzone. ApoE-dependent sterol efflux from macrophages is modulated by scavenger receptor class B type I expression. J. Lipid Res. 2002. 43: 375382
Supplementary key words: atherosclerosis, vascular wall
This article has been cited by other articles:
![]() |
M.-D. Wang, V. Franklin, and Y. L. Marcel In Vivo Reverse Cholesterol Transport From Macrophages Lacking ABCA1 Expression Is Impaired Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1837 - 1842. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. G. Yancey, W. G. Jerome, H. Yu, E. E. Griffin, B. E. Cox, V. R. Babaev, S. Fazio, and M. F. Linton Severely altered cholesterol homeostasis in macrophages lacking apoE and SR-BI J. Lipid Res., May 1, 2007; 48(5): 1140 - 1149. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. G. Yancey, H. Yu, M. F. Linton, and S. Fazio A Pathway-Dependent on ApoE, ApoAI, and ABCA1 Determines Formation of Buoyant High-Density Lipoprotein by Macrophage Foam Cells Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1123 - 1131. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. A. Pagler, S. Rhode, A. Neuhofer, H. Laggner, W. Strobl, C. Hinterndorfer, I. Volf, M. Pavelka, E. R. M. Eckhardt, D. R. van der Westhuyzen, et al. SR-BI-mediated High Density Lipoprotein (HDL) Endocytosis Leads to HDL Resecretion Facilitating Cholesterol Efflux J. Biol. Chem., April 21, 2006; 281(16): 11193 - 11204. [Abstract] [Full Text] [PDF] |
||||
![]() |
Z. H. Huang, M. L. Fitzgerald, and T. Mazzone Distinct Cellular Loci for the ABCA1-Dependent and ABCA1-Independent Lipid Efflux Mediated by Endogenous Apolipoprotein E Expression Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 157 - 162. [Abstract] [Full Text] [PDF] |
||||
![]() |
H. Yu, W. Zhang, P. G. Yancey, M. J. Koury, Y. Zhang, S. Fazio, and M. F. Linton Macrophage Apolipoprotein E Reduces Atherosclerosis and Prevents Premature Death in Apolipoprotein E and Scavenger Receptor-Class BI Double-Knockout Mice Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 150 - 156. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Daugherty, N. R. Webb, D. L. Rateri, and V. L. King Thematic review series: The Immune System and Atherogenesis. Cytokine regulation of macrophage functions in atherogenesis J. Lipid Res., September 1, 2005; 46(9): 1812 - 1822. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Fazio and M. F. Linton Interplay Between Apolipoprotein E and Scavenger Receptor Class B Type I Controls Coronary Atherosclerosis and Lifespan in the Mouse Circulation, June 28, 2005; 111(25): 3349 - 3351. [Full Text] [PDF] |
||||
![]() |
L. Yue, N. Rasouli, G. Ranganathan, P. A. Kern, and T. Mazzone Divergent Effects of Peroxisome Proliferator-activated Receptor {gamma} Agonists and Tumor Necrosis Factor {alpha} on Adipocyte ApoE Expression J. Biol. Chem., November 12, 2004; 279(46): 47626 - 47632. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. Van Eck, I. S. T. Bos, R. B. Hildebrand, B. T. Van Rij, and T. J.C. Van Berkel Dual Role for Scavenger Receptor Class B, Type I on Bone Marrow-Derived Cells in Atherosclerotic Lesion Development Am. J. Pathol., September 1, 2004; 165(3): 785 - 794. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. L. Trigatti, M. Krieger, and A. Rigotti Influence of the HDL Receptor SR-BI on Lipoprotein Metabolism and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., October 1, 2003; 23(10): 1732 - 1738. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. D. Covey, M. Krieger, W. Wang, M. Penman, and B. L. Trigatti Scavenger Receptor Class B Type I-Mediated Protection Against Atherosclerosis in LDL Receptor-Negative Mice Involves Its Expression in Bone Marrow-Derived Cells Arterioscler. Thromb. Vasc. Biol., September 1, 2003; 23(9): 1589 - 1594. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Rigotti, H. E. Miettinen, and M. Krieger The Role of the High-Density Lipoprotein Receptor SR-BI in the Lipid Metabolism of Endocrine and Other Tissues Endocr. Rev., June 1, 2003; 24(3): 357 - 387. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. S. Kiss, D. C. McManus, V. Franklin, W. L. Tan, A. McKenzie, G. Chimini, and Y. L. Marcel The Lipidation by Hepatocytes of Human Apolipoprotein A-I Occurs by Both ABCA1-dependent and -independent Pathways J. Biol. Chem., March 14, 2003; 278(12): 10119 - 10127. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |