Document Detail


Isolation of a somatic cell mutant resistant to the induction of apoptosis by oxidized low density lipoprotein.
MedLine Citation:
PMID:  10702300     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxidized low density lipoprotein (oxLDL) induces apoptosis in macrophages, smooth muscle cells, and endothelial cells. To elucidate the molecular mechanism of oxLDL-induced cytotoxicity and determine its tissue specificity, we have used Chinese hamster ovary (CHO)-K1 cells expressing human CD36 (CHO/CD36). Expression of CD36 rendered these cells susceptible to killing by oxLDL. This cytotoxicity was due to the induction of apoptosis. Therefore, CD36 expression is the only requirement for oxLDL-induced apoptosis. Oxysterols apparently mediate the cytotoxicity of oxLDL in macrophage foam cells and endothelial cells. 25-Hydroxycholesterol, at concentrations higher than 1 microg/ml, killed CHO-K1 cells, by apoptosis, in medium supplemented with serum as a source of cholesterol. These effects were not seen in a 25-hydroxycholesterol-resistant CHO/CD36 mutant (OX(R)), which was otherwise capable of undergoing apoptosis in response to staurosporine. This mutant was also resistant to killing by oxLDL, suggesting that oxysterols are at least partially responsible for the toxic effects of oxLDL. Oxysterol-induced apoptosis did not involve regulation of sterol regulatory element-binding protein proteolysis or the cholesterol biosynthetic pathway. 25-Hydroxycholesterol stimulated calcium uptake by CHO-K1 cells within 2 min after addition. Treatment of CHO or THP-1 (macrophage) cells with the calcium channel blocker nifedipine prevented 25-hydroxycholesterol induction of apoptosis. OX(R) showed no enhanced calcium uptake in response to 25-hydroxycholesterol.
Authors:
A E Rusiñol; L Yang; D Thewke; S R Panini; M F Kramer; M S Sinensky
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-04-03     Completed Date:  2000-04-03     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  7296-303     Citation Subset:  IM    
Affiliation:
Department Of Biochemistry and Molecular Biology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37614-0581, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD36 / physiology
Apoptosis / drug effects*
CHO Cells
Calcium / metabolism
Cricetinae
DNA-Binding Proteins / metabolism
Hydroxycholesterols / pharmacology
Lipoproteins, LDL / toxicity*
Mutation
Sterol Regulatory Element Binding Protein 2
Transcription Factors / metabolism
Transcription, Genetic
Transfection
Chemical
Reg. No./Substance:
0/Antigens, CD36; 0/DNA-Binding Proteins; 0/Hydroxycholesterols; 0/Lipoproteins, LDL; 0/Sterol Regulatory Element Binding Protein 2; 0/Transcription Factors; 0/oxidized low density lipoprotein; 2140-46-7/25-hydroxycholesterol; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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