Document Detail


Low-density lipoprotein induced actin cytoskeleton reorganization in endothelial cells: mechanisms of action.
MedLine Citation:
PMID:  11577705     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The inhibitory effects of the specific NADPH oxidase inhibitor, apocynin, and non-specific NADPH oxidase inhibitors, nordihydroguaiaretic acid (NDGA) and SKF525A, on the disruption of dense peripheral bands and formation of stress fibers in cultured human umbilical vein endothelial cells exposed to atherogenic low-density lipoprotein (LDL) levels has been investigated. Endothelial cells (EC) in vitro and in vivo exposed to high LDL-cholesterol levels have cytoskeletal remodeling with stress fiber formation and loss of dense peripheral bands. Cultured EC incubated with exogenously applied hydrogen peroxide (H2O2: 1 mM) have cytoskeletal structural changes much similar to those observed with high LDL exposure. Previous studies have 1) demonstrated that exposure to atherogenic LDL levels causes heightened EC H2O2 production, 2) identified the reactive oxygen species source, NADPH oxidase, in EC, and 3) shown that the specific NADPH oxidase inhibitor, apocynin, and non-specific NADPH oxidase inhibitors, NDGA and SKF525A, suppress H2O2 production increases in high LDL-perturbed EC. In the present study, the cytoskeletal structure of EC exposed to 330 mg/dl LDL-cholesterol, and incubated with or without apocynin, NDGA and SKF525A, was examined. Each of these compounds promoted the retention of dense peripheral bands and minimized stress fiber formation. These findings are consistent with NADPH oxidase and it's reactive oxygen species byproducts modulating the cytoskeleton reorganization observed in high LDL-induced EC perturbation.
Authors:
J A Holland; R A Goss; R W O'Donnell; M M Chang; D K Johnson; L M Ziegler
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Endothelium : journal of endothelial cell research     Volume:  8     ISSN:  1062-3329     ISO Abbreviation:  Endothelium     Publication Date:  2001  
Date Detail:
Created Date:  2001-09-26     Completed Date:  2002-02-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9412590     Medline TA:  Endothelium     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  117-35     Citation Subset:  IM    
Affiliation:
Department of Medicine, State University of New York Health Science Center Syracuse, 13210, USA. james.holland3@med.va.gov
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MeSH Terms
Descriptor/Qualifier:
Acetophenones / pharmacology
Actins / ultrastructure*
Animals
Aorta, Abdominal / ultrastructure
Aorta, Thoracic / ultrastructure
Arteriosclerosis / chemically induced,  pathology
Cells, Cultured
Endothelium, Vascular / cytology,  drug effects*,  metabolism,  ultrastructure*
Enzyme Inhibitors / pharmacology
Humans
Lipoproteins, LDL / pharmacology*
Male
Microfilaments / drug effects,  ultrastructure*
Microscopy, Fluorescence
NADPH Oxidase / antagonists & inhibitors
Nordihydroguaiaretic Acid / pharmacology
Perfusion
Proadifen / pharmacology
Rabbits
Umbilical Veins / cytology
Grant Support
ID/Acronym/Agency:
HL49573/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Acetophenones; 0/Actins; 0/Enzyme Inhibitors; 0/Lipoproteins, LDL; 302-33-0/Proadifen; 498-02-2/acetovanillone; 500-38-9/Nordihydroguaiaretic Acid; EC 1.6.3.1/NADPH Oxidase

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


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