Document Detail

7-Ketocholesterol is Not Cytotoxic to U937 Cells When Incorporated into Acetylated Low Density Lipoprotein.
MedLine Citation:
PMID:  22124807     Owner:  NLM     Status:  Publisher    
The growth of the necrotic core region within advanced atherosclerotic plaque is thought to be driven by oxidised low density lipoprotein (oxLDL)-induced death of macrophage cells. OxLDL and atherosclerotic plaque are rich in oxysterols, especially 7-ketocholesterol (7KC). As 7KC triggers cell death at physiological concentrations when added directly to the cell culture media, 7KC and other oxysterols have been suggested to be the main cytotoxic agent of oxLDL. We investigated this hypothesis by examining the toxicity of 7KC to monocyte-like U937 cells when incorporated into high-uptake non-toxic acetylated LDL (acLDL). Incorporation of 7KC into acLDL greatly reduced the oxysterol toxicity when compared with an equivalent amount of 7KC added directly to U937 cells. Enrichment of oxLDL with 7KC did not significantly enhance lipoprotein toxicity. OxLDL was highly cytotoxic yet generated only low levels of intracellular 7KC. In comparison, 7KC-acLDL generated high intracellular 7KC concentrations with little loss in cell viability. The data show that when incorporated into lipoprotein, 7KC cytotoxicity is greatly reduced, even though intracellular levels exceed those measured when cells are incubated with oxLDL, which suggests 7KC is not the significant toxic agent within oxLDL.
Lucy D Rutherford; Steven P Gieseg
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-29
Journal Detail:
Title:  Lipids     Volume:  -     ISSN:  1558-9307     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0060450     Medline TA:  Lipids     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Free Radical Biochemistry Laboratory, School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch, 8140, New Zealand.
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