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Enhanced DNA Binding and Activation of Transcription Factors NF-κB and AP-1 by Acetaldehyde in HEPG2 Cells

2000; Elsevier BV; Volume: 275; Issue: 19 Linguagem: Inglês

10.1074/jbc.275.19.14684

1083-351X

Juan José Mora Román, A. Giménez, José María Lluis, Marta Gassó, M Belen Rubio, Joan Caballería, Albert Parés, Joan Rodés, José C. Fernández–Checa,

Alcohol Consumption and Health Effects

Because transcription factors NF-κB and activator protein-1 (AP-1) are known to regulate gene expression, we have analyzed the role of acetaldehyde in the activation of NF-κB and AP-1 in HepG2 cells. Binding activity and transactivation of NF-κB and AP-1 were determined by gel retardation assays and transfection of a luciferase reporter construct controlled by κB and AP-1 binding sites, respectively. Acetaldehyde enhanced the DNA binding of NF-κB and AP-1 by 1 and 4 h, respectively, increasing the κB- and AP-1-dependent luciferase expression. Supershift assays revealed the presence of NF-κB heterodimers p65/p50 and p50/p52, whereas nuclear c-Jun levels correlated with the DNA binding of AP-1. The enhanced binding of NF-κB to DNA by acetaldehyde in intact cells was accompanied by the proteolytic degradation of IκB-α. 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-κB heterodimer p65/p50 in the absence of IκB-α degradation. Preincubation of HepG2 cells with protein kinase C inhibitors abolished the enhanced DNA binding of NF-κB and AP-1 caused by acetaldehyde. Hence, these findings uncover a previously unrecognized role for acetaldehyde in the activation of NF-κB and AP-1, which may be of relevance in the alcohol-induced liver disease.