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Titolo:
Enhanced DNA binding and activation of transcription factors NF-kappa B and AP-1 by acetaldehyde in HEPG2 cells
Autore:
Roman, J; Gimenez, A; Lluis, JM; Gasso, M; Rubio, M; Caballeria, J; Pares, A; Rodes, J; Fernandez-Checa, JC;
Indirizzi:
CSIC, Inst Malalt Digest, Liver Unit, Barcelona 08036, Spain CSIC Barcelona Spain 08036 lt Digest, Liver Unit, Barcelona 08036, Spain CSIC, Inst Invest Biomed August Pi Suner, Barcelona 08036, Spain CSIC Barcelona Spain 08036 iomed August Pi Suner, Barcelona 08036, Spain
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 19, volume: 275, anno: 2000,
pagine: 14684 - 14690
SICI:
0021-9258(20000512)275:19<14684:EDBAAO>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-NECROSIS-FACTOR; ALPHA(2)(I) COLLAGEN PROMOTER; KINASE-C ACTIVATION; GENE-TRANSCRIPTION; LIPID-PEROXIDATION; MITOCHONDRIAL GLUTATHIONE; OXIDATIVE STRESS; REDOX REGULATION; RAT HEPATOCYTES; STELLATE CELLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Fernandez-Checa, JC Hosp Clin & Prov Barcelona, Liver Unit, Villarroel 170, Barcelona, Spain Hosp Clin & Prov Barcelona Villarroel 170 Barcelona Spain
Citazione:
J. Roman et al., "Enhanced DNA binding and activation of transcription factors NF-kappa B and AP-1 by acetaldehyde in HEPG2 cells", J BIOL CHEM, 275(19), 2000, pp. 14684-14690

Abstract

Because transcription factors NF-kappa B and activator protein-1 (AP-1) are known to regulate gene expression, we have analyzed the role of acetaldehyde in the activation of NF-kappa B and AP-1 in HepG2 cells. Binding activity and transactivation of NF-kappa B and AP-1 were determined by gel retardation assays and transfection of a luciferase reporter construct controlledby kappa B and AP-1 binding sites, respectively. Acetaldehyde enhanced theDNA binding of NF-kappa B and AP-1 by 1 and 4 h, respectively, increasing the kappa B- and AP-1-dependent luciferase expression. Supershift assays revealed the presence of NF-kappa B heterodimers p65/p50 and p50/p52, whereasnuclear c-Jun levels correlated with the DNA binding of AP-1. The enhancedbinding of NF-kappa B to DNA by acetaldehyde in intact cells was accompanied by the proteolytic degradation of I kappa B-alpha. However, the additionof acetaldehyde to cytostolic extracts from untreated Hep G2 cells did notaffect the DNA binding of AP-1 but activated the NF-kappa B heterodimer p65/p50 in the absence of I kappa B-alpha degradation. Preincubation of HepG2cells with protein kinase C inhibitors abolished the enhanced DNA binding of NF-kappa B and AP-1 caused by acetaldehyde. Hence, these findings uncover a previously unrecognized role for acetaldehyde in the activation of NF-kappa B and AP-1, which may be of relevance in the alcohol-induced liver disease.

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Documento generato il 30/11/20 alle ore 09:50:42