Document Detail

Role of 4-hydroxy-2,3-nonenal in the pathogenesis of fibrosis.
MedLine Citation:
PMID:  16403983     Owner:  NLM     Status:  MEDLINE    
Transient activation of fibroblasts or fibroblast-like cells to proliferate and to produce elevated quantities of extracellular matrix is essential to fibrosis. This activation is regulated by several cytokines produced by various inflammation-associated cells. Among these, transforming growth factor beta1 (TGFbeta1) is considered of major importance. Many studies have shown that lipid peroxidation play a key role in the initiation and progression of fibrosis in different organs. In fact, 4-hydroxy-2,3-nonenal (HNE), the major aldehydic product of lipid peroxidation, is able to induce TGFbeta1 expression and synthesis, and activation of activator protein-1 (AP-1) transcription factor. In this study, using the murine macrophage line J774-A1, we show that these effects are strictly related to the chemical structure of HNE, since neither 2-nonenal nor nonanal are biologically active to the same extent. Moreover, we demonstrate that HNE can indeed contribute to the onset of fibrosis by stimulating AP-1 binding to DNA and consequently inducing TGFbeta1 expression, since thiol-group reagents, such as N-ethylmaleimide and 4-(chloro-mercuri)-benzenesulfonic acid, that down-modulate HNE entrance and localisation inside the cell, prevent both phenomena. The possibility to control fibrogenic cytokine levels by means of antioxidant or dietetic treatments opens new potential pharmacological and nutritional horizons in the treatment of many chronic diseases characterised by excessive fibrosis.
Elena Chiarpotto; Laura Castello; Gabriella Leonarduzzi; Fiorella Biasi And; Giuseppe Poli
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  BioFactors (Oxford, England)     Volume:  24     ISSN:  0951-6433     ISO Abbreviation:  Biofactors     Publication Date:  2005  
Date Detail:
Created Date:  2006-01-11     Completed Date:  2006-05-23     Revised Date:  2006-11-20    
Medline Journal Info:
Nlm Unique ID:  8807441     Medline TA:  Biofactors     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  229-36     Citation Subset:  IM    
Department of Clinical and Biological Sciences, University of Torino, Regione Gonzole 10, 10043 Orbassano (TO), Italy.
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MeSH Terms
Aldehydes / chemistry,  pharmacology*
Cell Line
DNA / metabolism
Electrophoretic Mobility Shift Assay
Gene Expression / drug effects
Lipid Peroxidation
Macrophages / drug effects*,  metabolism
Proteins / genetics
Structure-Activity Relationship
Transcription Factor AP-1 / metabolism
Reg. No./Substance:
0/Aldehydes; 0/Proteins; 0/Transcription Factor AP-1; 124-19-6/nonanal; 2463-53-8/2-nonenal; 29343-52-0/4-hydroxy-2-nonenal; 9007-49-2/DNA

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

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