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) 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 Krimbou, L. Articles by Cohn, J. S. Search for Related Content PubMed PubMed Citation Articles by Krimbou, L. Articles by Cohn, J. S. Social Bookmarking                      What's this?

The Journal of Lipid Research, Vol. 39, 2373-2386, December 1998
Copyright © 1998 by Lipid Research, Inc.

Original Article

Association of apolipoprotein E with ₂-macroglobulin in human plasma

Correspondence to: Jeffrey S. Cohn.

Apolipoprotein (apo) E plays a central role in the transport of lipids among different organs and cell types, whereas ₂-macroglobulin (₂M) is responsible for the binding and inactivation of plasma proteases, as well as the transport of various cytokines, growth factors, and hormones. In the present study, evidence is presented for direct binding of apoE with ₂M in human plasma, based on the observation that two-dimensional non-denaturing gradient gel electrophoretic separation of plasma resulted in co-migration of apoE with ₂M in a complex intermediate in size (18.5 nm in diameter) between low (LDL) and high density lipoproteins (HDL). ApoE associated with ₂M could be immunoprecipitated from plasma with anti-human ₂M antiserum. Purified apoE, labeled with ¹²⁵I, bound to native and methylamine-activated ₂M (₂M-MA) in vitro in a time- and concentration-dependent manner. ApoE bound to ₂M-MA with greater affinity than ₂M. The binding of apoE to both ₂M and ₂M-MA did not depend on the presence of lipid. Ingestion of an oral fat load resulted in a reduction in the amount of apoE associated with ₂M. Sphingomyelin vesicles and very low density lipoproteins (VLDL), but not phosphatidylcholine vesicles or HDL₃, inhibited the in vitro binding of ¹²⁵I-labeled apoE3 to ₂M and ₂M-MA. Binding of ¹²⁵I-labeled apoE3 was also partially inhibited by an excess of platelet-derived growth factor and ß-amyloid protein, but not interferon-. Subjects with an apoE 4/4 phenotype had less apoE associated with ₂M in plasma than subjects with an apoE 3/3 or 2/2 phenotype, corresponding to reduced in vitro binding of apoE4 with ₂M or ₂M-MA.

Although the functional significance of apoE binding to ₂M remains to be determined, the present results demonstrate that: 1) apoE is non-covalently bound to ₂M in human plasma, 2) ₂M-MA has a greater capacity to bind apoE than ₂M, 3) various proteins or lipoproteins known to bind apoE or ₂M can potentially affect the interaction of apoE with ₂M, and 4) association of apoE with ₂M or ₂M-MA is dependent on apoE phenotype.—Krimbou, L., M. Tremblay, J. Davignon, and J. S. Cohn. Association of apolipoprotein E with ₂-macroglobulin in human plasma. J. Lipid Res. 1998. 39: 2373–2386.

Supplementary key words: atherosclerosis, Alzheimer's disease, high density lipoprotein, LRP

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

This article has been cited by other articles:

				M.-F. Galliano, E. Toulza, H. Gallinaro, N. Jonca, A. Ishida-Yamamoto, G. Serre, and M. Guerrin A Novel Protease Inhibitor of the {alpha}2-Macroglobulin Family Expressed in the Human Epidermis J. Biol. Chem., March 3, 2006; 281(9): 5780 - 5789. [Abstract] [Full Text] [PDF]

				A. Nilsson and R.-D. Duan Absorption and lipoprotein transport of sphingomyelin J. Lipid Res., January 1, 2006; 47(1): 154 - 171. [Abstract] [Full Text] [PDF]

				L. Krimbou, M. Denis, B. Haidar, M. Carrier, M. Marcil, and J. Genest Jr. Molecular interactions between apoE and ABCA1: impact on apoE lipidation J. Lipid Res., May 1, 2004; 45(5): 839 - 848. [Abstract] [Full Text] [PDF]

				M. Denis, B. Haidar, M. Marcil, M. Bouvier, L. Krimbou, and J. Genest Jr. Molecular and Cellular Physiology of Apolipoprotein A-I Lipidation by the ATP-binding Cassette Transporter A1 (ABCA1) J. Biol. Chem., February 27, 2004; 279(9): 7384 - 7394. [Abstract] [Full Text] [PDF]

				A. J. Saunders, L. Bertram, K. Mullin, A. J. Sampson, K. Latifzai, S. Basu, J. Jones, D. Kinney, L. MacKenzie-Ingano, S. Yu, et al. Genetic association of Alzheimer's disease with multiple polymorphisms in alpha-2-macroglobulin Hum. Mol. Genet., November 1, 2003; 12(21): 2765 - 2776. [Abstract] [Full Text] [PDF]

				L. Krimbou, M. Marcil, H. Chiba, and J. Genest Jr. Structural and functional properties of human plasma high density-sized lipoprotein containing only apoE particles J. Lipid Res., May 1, 2003; 44(5): 884 - 892. [Abstract] [Full Text] [PDF]

				J. S. Cohn, M. Tremblay, R. Batal, H. Jacques, L. Veilleux, C. Rodriguez, P. H. R. Barrett, D. Dubreuil, M. Roy, L. Bernier, et al. Effect of atorvastatin on plasma apoE metabolism in patients with combined hyperlipidemia J. Lipid Res., September 1, 2002; 43(9): 1464 - 1471. [Abstract] [Full Text] [PDF]

				C. Marcoux, M. Tremblay, K. Nakajima, J. Davignon, and J. S. Cohn Characterization of remnant-like particles isolated by immunoaffinity gel from the plasma of type III and type IV hyperlipoproteinemic patients J. Lipid Res., April 1, 1999; 40(4): 636 - 647. [Abstract] [Full Text]