Advertisement
J. Lipid Res.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.M700217-JLR200 on August 25, 2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
M700217-JLR200v1
48/12/2571    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wu, D.
Right arrow Articles by Guo, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wu, D.
Right arrow Articles by Guo, Z.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Journal of Lipid Research, Vol. 48, 2571-2578, December 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Apolipoprotein E-deficient lipoproteins induce foam cell formation by downregulation of lysosomal hydrolases in macrophages

DongFang Wu*, Chakradhari Sharan*, Hong Yang*, J. Shawn Goodwin{dagger}, Lichun Zhou*, Gregory A. Grabowski§, Hong Du§ and ZhongMao Guo1,*

* Department of Cardiovascular Biology, Meharry Medical College, Nashville, TN 37208
{dagger} Department of Cancer Biology, Meharry Medical College, Nashville, TN 37208
§ Division and Program in Human Genetics, Children's Hospital Research Foundation, Cincinnati, OH 45229

Published, JLR Papers in Press, August 25, 2007.

1 To whom correspondence should be addressed. e-mail: zguo{at}mmc.edu

Apolipoprotein E (apoE) deficiency has been suggested to induce foam cell formation. Using lipoproteins obtained from wild-type mice and apoE-deficient mice expressing apoB-48 but not apoB-100, we studied apoE-deficient lipoprotein-induced changes in lipoprotein catabolism and protein expression in mouse peritoneal macrophages (MPMs). Our data demonstrate that incubation of MPMs with apoE-deficient lipoproteins induced intracellular lipoprotein, cholesteryl ester, and triglyceride accumulation, which was associated with a time-related decline in apoE-deficient lipoprotein degradation in MPMs. Confocal microscopy analysis indicated that the accumulated lipids were localized in lysosomes. ApoE-deficient lipoproteins reduced the protein levels of lysosomal acid lipase, cathepsin B, and cation-dependent mannose 6 phosphate receptor (MPR46). Exogenous apoE reduced apoE-deficient lipoprotein-induced lipid accumulation and attenuated the suppressive effect of apoE-deficient lipoproteins on lysosomal hydrolase and MPR46 expression. Although oxidized lipoproteins also increased lipid contents in MPMs, exogenous apoE could not attenuate oxidized lipoprotein-induced lipid accumulation. Our in vivo studies also showed that feeding apoE-deficient mice a high-fat diet resulted in cholesteryl ester and triglyceride accumulation and reduced lysosomal hydrolase expression in MPMs. These data suggest that apoE-deficient lipoproteins increase cellular lipid contents through pathways different from those activated by oxidized lipoproteins and that reducing lysosomal hydrolases in macrophages might be a mechanism by which apoE-deficient lipoproteins result in intralysosomal lipoprotein accumulation, thereby inducing foam cell formation.

Abbreviations: apoB, apolipoprotein B; apoB-48R, apolipoprotein B-48 receptor; E–/B48, apolipoprotein E-deficient, apolipoprotein B-48-containing lipoprotein; EC, esterified cholesterol; FC, free cholesterol; LDLR, low density lipoprotein receptor; MPM, mouse peritoneal macrophage; MPR46, cation-dependent mannose 6 phosphate receptor; SR, scavenger receptor; SR-A, scavenger receptor class A; SR-BI, scavenger receptor class B type I; TBARS, thiobarbituric acid-reacting substances

Supplementary key words oxidized lipoproteins • cholesterol ester • mannose 6 phosphate receptor


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


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
D. Wu, H. Yang, Y. Zhao, C. Sharan, J. S. Goodwin, L. Zhou, Y. Guo, and Z. Guo
2-Aminopurine Inhibits Lipid Accumulation Induced by Apolipoprotein E-Deficient Lipoprotein in Macrophages: Potential Role of Eukaryotic Initiation Factor-2{alpha} Phosphorylation in Foam Cell Formation
J. Pharmacol. Exp. Ther., August 1, 2008; 326(2): 395 - 405.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Chem.Home page
A. T. Remaley
Commentary
Clin. Chem., March 1, 2008; 54(3): 610 - 611.
[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 
Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement