J. Lipid Res. Did you know there is a large type edition? Click here.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on September 1, 2005

Papers In Press, published online ahead of print July 1, 2005
J. Lipid Res., doi:10.1194/jlr.M500101-JLR200
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
M500101-JLR200v1
46/9/1933    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Freeman, N. E.
Right arrow Articles by Thewke, D. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Freeman, N. E.
Right arrow Articles by Thewke, D. P.
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?

Submitted on March 17, 2005
Revised on June 7, 2005
Accepted on June 22, 2005

Acyl-CoA: Cholesterol acyltransferase promotes oxidized LDL/oxysterol-induced apoptosis in macrophages

Natalie E. Freeman, Antonio E. Rusinol, MacRae Linton, David L. Hachey, Sergio Fazio, Michael S. Sinensky, and Douglas P. Thewke

Biochemistry & Molecular Biology, East Tennessee State University, Johnson City, TN 37614

Corresponding Author: thewke{at}etsu.edu

7-ketocholesterol (7KC) is a cytotoxic component of oxidized low-density lipoproteins (oxLDL) and induces apoptosis in macrophages by a mechanism involving activation of cytosolic phospholipase A2 (cPLA2). In the current study, we examined the role of acyl-CoA: cholesterol acyltransferase (ACAT) in 7KC-induced and oxLDL-induced apoptosis in murine macrophages. An ACAT inhibitor, Sandoz 58-035, suppressed 7KC-induced apoptosis in P388D1 cells and both 7KC-induced and oxLDL-induced apoptosis in mouse peritoneal macrophages (MPMs). Furthermore, in comparison to wild type MPMs, ACAT-1 deficient MPMs demonstrated significant resistance to both 7KC-induced and oxLDL-induced apoptosis. Macrophages treated with 7KC accumulated ACAT-derived [14C]cholesteryl and [3H]7-ketocholesteryl esters. Tandem LC/MS revealed that the 7KC esters contained primarily saturated and monounsaturated fatty acids. An inhibitor of cPLA2, arachidonyl trifluoromethyl ketone, prevented the accumulation of 7KC esters and inhibited 7KC-induced apoptosis in P388D1 cells. The decrease in 7KC ester accumulation produced by inhibition of cPLA2 was reversed by supplementing with either oleic or arachidonic acid; however, only arachidonic acid supplementation restored induction of apoptosis by 7KC. These results suggest that 7KC not only initiates the apoptosis pathway by activating cPLA2, as we have previously reported, but also participates in the downstream signaling pathway when esterified by ACAT to form 7KC-arachidonate.


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. Lipid Res.Home page
N. E. Freeman-Anderson, T. G. Pickle, C. D. Netherland, A. Bales, N. E. Buckley, and D. P. Thewke
Cannabinoid (CB2) receptor deficiency reduces the susceptibility of macrophages to oxidized LDL/oxysterol-induced apoptosis
J. Lipid Res., November 1, 2008; 49(11): 2338 - 2346.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.