Document Detail

OxLDL-induced macrophage cytotoxicity is mediated by lysosomal rupture and modified by intralysosomal redox-active iron.
MedLine Citation:
PMID:  9925031     Owner:  NLM     Status:  MEDLINE    
Oxidized low density lipoprotein (oxLDL) is believed to play a central role in atherogenesis. LDL is oxidized in the arterial intima by mechanisms that are still only partially understood. OxLDL is then taken up by macrophages through scavenger receptor-mediated endocytosis, which then leads to cellular damage, including apoptosis. The complex mechanisms by which oxLDL induces cell injury are mostly unknown. This study has demonstrated that oxLDL-induced damage of macrophages is associated with iron-mediated intralysosomal oxidative reactions, which cause partial lysosomal rupture and ensuing apoptosis. This series of events can be prevented by pre-exposing cells to the iron-chelator, desferrioxamine (DFO), whereas it is augmented by pretreating the cells with a low molecular weight iron complex. Since both DFO and the iron complex would be taken up by endocytosis, and thus directed to the lysosomal compartment, the results suggest that the normal contents of lysosomal low molecular weight iron may play an important role in oxLDL-induced cell damage, presumably by catalyzing intralysosomal fragmentation of lipid peroxides and the formation of toxic aldehydes and oxygen-centered radicals.
W Li; X M Yuan; U T Brunk
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Free radical research     Volume:  29     ISSN:  1071-5762     ISO Abbreviation:  Free Radic. Res.     Publication Date:  1998 Nov 
Date Detail:
Created Date:  1999-03-18     Completed Date:  1999-03-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9423872     Medline TA:  Free Radic Res     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  389-98     Citation Subset:  IM    
Department of Neurobiology and Locomotion, and Clinical Research Centre, Faculty of Health Sciences, Linköping University, Sweden.
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MeSH Terms
Apoptosis / drug effects*
Cell Division / drug effects
Cell Line
Cell Survival / drug effects
DNA Fragmentation
Deferoxamine / pharmacology
Iron / pharmacology*
Iron Chelating Agents / pharmacology
Lipoproteins, LDL / pharmacology*
Lysosomes / drug effects*
Macrophages / drug effects*,  ultrastructure*
Reg. No./Substance:
0/Iron Chelating Agents; 0/Lipoproteins, LDL; 0/oxidized low density lipoprotein; 70-51-9/Deferoxamine; 7439-89-6/Iron

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