Document Detail


Enhanced DNA binding and activation of transcription factors NF-kappa B and AP-1 by acetaldehyde in HEPG2 cells.
MedLine Citation:
PMID:  10799556     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Because transcription factors NF-kappaB and activator protein-1 (AP-1) are known to regulate gene expression, we have analyzed the role of acetaldehyde in the activation of NF-kappaB and AP-1 in HepG2 cells. Binding activity and transactivation of NF-kappaB and AP-1 were determined by gel retardation assays and transfection of a luciferase reporter construct controlled by kappaB and AP-1 binding sites, respectively. Acetaldehyde enhanced the DNA binding of NF-kappaB and AP-1 by 1 and 4 h, respectively, increasing the kappaB- and AP-1-dependent luciferase expression. Supershift assays revealed the presence of NF-kappaB heterodimers p65/p50 and p50/p52, whereas nuclear c-Jun levels correlated with the DNA binding of AP-1. The enhanced binding of NF-kappaB to DNA by acetaldehyde in intact cells was accompanied by the proteolytic degradation of IkappaB-alpha. However, the addition of acetaldehyde to cytostolic extracts from untreated Hep G2 cells did not affect the DNA binding of AP-1 but activated the NF-kappaB heterodimer p65/p50 in the absence of IkappaB-alpha degradation. Preincubation of HepG2 cells with protein kinase C inhibitors abolished the enhanced DNA binding of NF-kappaB and AP-1 caused by acetaldehyde. Hence, these findings uncover a previously unrecognized role for acetaldehyde in the activation of NF-kappaB and AP-1, which may be of relevance in the alcohol-induced liver disease.
Authors:
J Román; A Giménez; J M Lluis; M Gassó; M Rubio; J Caballeria; A Parés; J Rodés; J C Fernández-Checa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-06-08     Completed Date:  2000-06-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  14684-90     Citation Subset:  IM    
Affiliation:
Liver Unit, Institut Malalties Digestives and Instituto de Investigaciones Biomedicas August Pi Suñer, Consejo Superior de Investigaciones Cientificas, Barcelona 08036, Spain.
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MeSH Terms
Descriptor/Qualifier:
Acetaldehyde / pharmacology*
Base Sequence
Cytosol / drug effects,  metabolism
DNA / metabolism*
Gene Expression Regulation
Humans
NF-kappa B / metabolism*
Phosphorylation
Protein Binding
Protein Kinase C / metabolism
Transcription Factor AP-1 / metabolism*
Transcriptional Activation
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
AA 09526/AA/NIAAA NIH HHS; AA11999-01/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/NF-kappa B; 0/Transcription Factor AP-1; 75-07-0/Acetaldehyde; 9007-49-2/DNA; EC 2.7.11.13/Protein Kinase C

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