Biogenic 4-hydroxy-2-nonenal activates transcription factor AP-1 but not NF-kappa B in cells of the macrophage lineage.
A large spectrum of pro-oxidant agents, including molecules with lipoperoxidative effect, can modulate gene expression through modification of the DNA binding activity of the transcription factors activator protein 1 (AP-1) and nuclear factor kappa B (NF-kappa B). In this study the effect on these redox-sensitive factors by 4-hydroxy-2-nonenal (HNE), a major aldehydic product of lipid peroxidation, was examined in two cell lines of the macrophage type. Incubation in the presence of microM concentrations of the aldehyde led to a rapid increase of AP-1 binding with a transient maximum 30 min from HNE addition to the culture medium in both cell lines. On the contrary, HNE did not stimulate nuclear translocation of NF-kappa B. The diverging effect of HNE on the two transcription factors is likely related to the demonstrated differential activation pathway of AP-1 and NF-kappa B in macrophages. The HNE-induced activation of AP-1 suggests the aldehyde's involvement in the regulatory mechanisms of cell proliferation and differentiation.
Camandola
S
S
Department of Experimental Medicine and Oncology, University of Torino, Italy.
Scavazza
A
A
Leonarduzzi
G
G
Biasi
F
F
Chiarpotto
E
E
Azzi
A
A
Poli
G
G
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003432:Cross-Linking Reagents; D006801:Humans; D007700:Kinetics; D015227:Lipid Peroxidation; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000447:Aldehydes; D003432:Cross-Linking Reagents; D016328:NF-kappa B; D018808:Transcription Factor AP-1; C027576:4-hydroxy-2-nonenal; D013755:Tetradecanoylphorbol Acetate