Affiliations: Department of Experimental Medicine and Oncology, University of Torino, Italy | CNR Centre for Immunogenetics and Experimental Oncology, Torino, Italy | Institute for Biochemistry and Molecular Biology, University of Bern, Switzerland
Note: [] Correspondence to: Prof. Giuseppe Poli, Dipartimento di Medicina ed Oncologia Sperimentale, Sezione di Patologia Generale, Corso Raffaello, 30, 10125 Torino, Italy. Tel.: 0039/11/6707781; Fax: 0039/11/6707753; E‐mail: giuseppe. [email protected].
Abstract: 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‐\kappaB). 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 \muM 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‐\kappaB. The diverging effect of HNE on the two transcription factors is likely related to the demonstrated differential activation pathway of AP‐1 and NF‐\kappaB in macrophages. The HNE‐induced activation of AP‐1 suggests the aldehyde’s involvement in the regulatory mechanisms of cell proliferation and differentiation.
