Document Detail

Induction of ubiquitin-conjugating enzyme by aggregated low density lipoprotein in human macrophages and its implications for atherosclerosis.
MedLine Citation:
PMID:  10634809     Owner:  NLM     Status:  MEDLINE    
Recently, we have found that aggregated low density lipoprotein (agLDL) inhibits apoptosis of lipid-bearing macrophages, thereby facilitating foam cell formation and atherosclerosis. To clarify the mechanisms by which agLDL inhibits apoptosis of macrophages, we isolated the genes specifically induced by agLDL by using a subtraction-based cloning strategy. One of the cloned genes, termed low density lipoprotein (LDL)-inducible gene (LIG), encodes a human homologue of bovine ubiquitin-conjugating enzyme E2-25K. Although LIG mRNA was ubiquitously expressed among human tissues, including hematopoietic cells, the abundance of transcripts was markedly increased by agLDL treatment in activated monocytes. LIG mRNA expression was not enhanced by nonatherogenic lipoproteins such as native LDL and high density lipoprotein, suggesting a role in atherosclerosis. Polyubiquitination of intracellular proteins was observed in monocytes cultured with agLDL, which coincided with upregulation of LIG. Furthermore, ubiquitin-dependent degradation of p53, an inducer of apoptosis, was accompanied by LIG induction in agLDL-treated monocytes. The antiapoptotic effect of agLDL was abrogated by a specific proteasome inhibitor, which also increased the half-life of p53 in monocytes. These results suggest that LIG contributes to foam cell formation by the suppression of apoptosis of lipid-bearing macrophages through ubiquitination and subsequent degradation of p53.
J Kikuchi; Y Furukawa; N Kubo; A Tokura; N Hayashi; M Nakamura; M Matsuda; I Sakurabayashi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  20     ISSN:  1079-5642     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-01-28     Completed Date:  2000-01-28     Revised Date:  2008-09-13    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  128-34     Citation Subset:  IM    
Division of Molecular Hemopoiesis, Center for Molecular Medicine, Jichi Medical School, Tochigi, Japan.
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MeSH Terms
Amino Acid Sequence
Arteriosclerosis / etiology*,  genetics,  metabolism*
Base Sequence
DNA, Complementary / genetics
Foam Cells / metabolism
Gene Expression
Ligases / biosynthesis*,  genetics
Lipoproteins, LDL / pharmacology*
Macrophages / drug effects*,  metabolism*
Molecular Sequence Data
Monocytes / drug effects,  metabolism
RNA, Messenger / genetics,  metabolism
Tumor Suppressor Protein p53 / metabolism
Ubiquitin-Conjugating Enzymes*
Ubiquitins / metabolism
Reg. No./Substance:
0/DNA, Complementary; 0/Lipoproteins, LDL; 0/RNA, Messenger; 0/Tumor Suppressor Protein p53; 0/Ubiquitins; EC 6.-/Ligases; EC protein, human; EC Enzymes

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