Document Detail


Regulation of macrophage-specific gene expression by degenerated lipoproteins.
MedLine Citation:
PMID:  10675012     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effect of aggregated low-density lipoprotein (agLDL) on cell viability and macrophage-specific gene expression using human peripheral blood monocytes in culture was investigated. AgLDL suppressed activation-induced cell death of phorbol ester-treated macrophages. The inhibition of apoptosis was accompanied by downregulation of apoptosis-promoting proteases, including interleukin-1beta-converting enzyme (ICE) and CPP32 and upregulation of anti-apoptotic cytokine (interleukin-1beta (IL-1beta)). In contrast, macrophage-colony stimulating factor (M-CSF) enhanced cell death of lipid-bearing macrophages, suggesting that the anti-atherogenic action of M-CSF is at least in part mediated through apoptotic elimination of macrophages. Then, we attempted to isolate the genes specifically induced by agLDL in macrophages using a subtraction-based cloning strategy. One of the genes isolated, termed LIG (LDL-inducible gene), encodes a human homolog of E2 ubiquitin-conjugating enzyme. Ubiquitination of multiple intracellular proteins was observed in agLDL-treated macrophages, which coincided with upregulation of LIG. These results suggest that LIG acts as a direct mediator of foam cell formation through polyubiquitination and subsequent degradation of cellular proteins with apoptosis-inducing properties. The regulation of apoptosis by macrophage-specific gene expression may contribute to foam cell formation and atherosclerosis.
Authors:
Y Furukawa; N Kubo; J Kikuchi; A Tokura; N Fujita; I Sakurabayashi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Electrophoresis     Volume:  21     ISSN:  0173-0835     ISO Abbreviation:  Electrophoresis     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-03-10     Completed Date:  2000-03-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8204476     Medline TA:  Electrophoresis     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  338-46     Citation Subset:  IM    
Affiliation:
Division of Molecular Hemopoiesis, Center for Molecular Medicine, Jichi Medical School, Tochigi, Japan. furuyu@jichi.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects,  genetics
Cells, Cultured
Gene Expression Regulation / drug effects*
Humans
Lipoproteins, LDL / pharmacology*
Macrophage Activation / drug effects*,  genetics
Macrophages / drug effects*,  physiology*
Protein Biosynthesis
Proteins / genetics
Chemical
Reg. No./Substance:
0/Lipoproteins, LDL; 0/Proteins

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


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