Molecular mechanisms implicated in galectin-1-induced apoptosis: activation of the AP-1 transcription factor and downregulation of Bcl-2

Galectins are emerging as a new class of bioactive molecules with specific immunomodulatory properties. Galectin-1 (Gal-1), a member of this family, h as been shown to induce apoptosis of mature T cells and immature thymocytes . To gain insight into the Intracellular signals transduced by Gal-1 upon b inding to mature T cells, we investigated whether this protein triggered ac tivation of the dimeric AP-1 transcription factor. A marked increase in the binding of nuclear extracts to synthetic oligonucleotides containing the A P-1 consensus sequence, could be detected by an electrophoretic mobility sh ift assay, when T cells were cultured for 30 min in the presence of Gal-1. This DNA-binding activity was preceded by a rapid increase in the levels of c-Jun mRNA, as determined by Northern blot analysis. Requirement of AP-1 f or Gal-1-induced apoptosis was confirmed by the dose-dependent reduction on the level of DNA fragmentation observed when cells were pre-treated with c urcumin (an inhibitor of AP-1 activation) before exposure to Gal-1. Finally , evidence is also provided by Western blot analysis, showing that Gal-1 in hibits Concanavalin A (Con A) induction of Bcl-2 protein. Results presented in this study provide the first experimental evidence regarding AP-1 and B cl-2 as targets of the signal transduction pathway triggered by Gal-1 and s et the basis for a more in depth understanding of the molecular mechanisms of T-cell death regulation.