Document Detail

Oxidized low-density lipoprotein (oxLDL) triggers hypoxia-inducible factor-1alpha (HIF-1alpha) accumulation via redox-dependent mechanisms.
MedLine Citation:
PMID:  12586627     Owner:  NLM     Status:  MEDLINE    
Oxidized low-density lipoprotein (oxLDL) and macrophages play a central role in atherosclerosis. Here, we obtained evidence that oxLDL induced hypoxia-inducible factor-1alpha (HIF-1alpha) protein accumulation in human macrophages (Mono-Mac-6) under normoxia. HIF-1alpha accumulation was attenuated by pretreatment with the antioxidant N-acetyl-L-cysteine (NAC), the nitric oxide (NO) donor S-nitrosoglutathione (GSNO), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors such as diphenyleniodonium (DPI) or 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), thus implicating the contribution of oxLDL-generated reactive oxygen species (ROS). Whereas oxLDL did not modulate HIF-1alpha mRNA levels, experiments with cycloheximide pointed to a translational mechanism in oxLDL action. HIF-1-dependent luciferase reporter gene analysis underscored HIF-1 transactivation. Our results indicate that oxLDL induced HIF-1alpha accumulation and HIF-1-dependent reporter gene activation in human macrophages via a redox-mediated pathway. This finding may suggest a role of HIF-1 in atherosclerosis and oxLDL-induced pathogenesis.
Vladimir A Shatrov; Vadim V Sumbayev; Jie Zhou; Bernhard Brüne
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-02-13
Journal Detail:
Title:  Blood     Volume:  101     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-05     Completed Date:  2004-02-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4847-9     Citation Subset:  AIM; IM    
Faculty of Biology, Department of Cell Biology, University of Kaiserslautern, Germany.
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MeSH Terms
Acetylcysteine / pharmacology
Antioxidants / pharmacology
Cell Line
Enzyme Inhibitors / pharmacology
Gene Expression / drug effects
Hypoxia-Inducible Factor 1, alpha Subunit
Lipoproteins, LDL / pharmacology*
Macrophages / metabolism
NADPH Oxidase / antagonists & inhibitors
Nitric Oxide Donors / pharmacology
Onium Compounds / pharmacology
RNA, Messenger / analysis
Reactive Oxygen Species / metabolism
Reverse Transcriptase Polymerase Chain Reaction
S-Nitrosoglutathione / pharmacology
Transcription Factors / biosynthesis*,  genetics
Reg. No./Substance:
0/Antioxidants; 0/Enzyme Inhibitors; 0/HIF1A protein, human; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Lipoproteins, LDL; 0/Nitric Oxide Donors; 0/Onium Compounds; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/Transcription Factors; 0/oxidized low density lipoprotein; 244-54-2/diphenyleneiodonium; 57564-91-7/S-Nitrosoglutathione; 616-91-1/Acetylcysteine; EC Oxidase

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

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