INVESTIGADORES
SOTOMAYOR Claudia Elena
artículos
Título:
Molecular mechanisms implicated in galectin-1-induced
Autor/es:
RABINOVICH GA; ALONSO CR; SOTOMAYOR CE; DURAND S; BOCCO JL; RIERA CM
Revista:
CELL DEATH AND DIFFERENTIATION
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Año: 2000 vol. 7 p. 747 - 753
ISSN:
1350-9047
Resumen:
Galectins are emerging as a new class of bioactivemolecules
with specific immunomodulatory properties. Galectin-1 (Gal-
1), a member of this family, has been shown to induce
apoptosis of mature T cells and immature thymocytes. To
gain insight into the intracellular signals transduced by Gal-1
upon binding to mature T cells, we investigated whether this
protein triggered activation of the dimeric AP-1 transcription
factor. A marked increase in the binding of nuclear extracts to
synthetic oligonucleotides containing the AP-1 consensus
sequence, could be detected by an electrophoretic mobility
shift 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
for Gal-1-induced apoptosis was confirmed by the dosedependent
reduction on the level of DNA fragmentation
observed when cells were pre-treated with curcumin (an
inhibitor of AP-1 activation) before exposure to Gal-1. Finally,
evidence is also provided by Western blot analysis, showing
that Gal-1 inhibits Concanavalin A (Con A) induction of Bcl-2
protein. Results presented in this study provide the first
experimental evidence regarding AP-1 and Bcl-2 as targets of
the signal transduction pathway triggered by Gal-1 and set
the basis for a more in depth understanding of the molecular
mechanisms of T-cell death regulation.