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

Abstract

Galectins are emerging as a new class of bioactive molecules 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. Cell Death and Differentiation (2000) 7, 747 ± 753.

Astrocyte reactivity after brain injury—: The role of galectins 1 and 3

“…Besides regulation of cell cycle, exogenously added Gal‐1 also exerts effects through interaction with integrins (Astorgues‐Xerri et al, 2014; Moiseeva et al, 2003), such as activating proapoptotic α5β1‐integrin signaling (Sanchez‐Ruderisch et al, 2011). Gal‐1‐induced apoptosis involves several intracellular mediators including the transcription factor AP1 and the downregulation of Bcl2 protein production (Hahn et al, 2004; Rabinovich et al, 2000; Walzel et al, 2000). Taking into account that α5β1 integrin is an important mediator of microglial activation (Milner et al, 2007), cell surface presentation of Gal‐1 may be implicated in the α5β1‐integrin signaling also leading to death of microglia, consistent with our in vitro observations.…”

ΔFosB, but not FosB, induces delayed apoptosis independent of cell proliferation in the Rat1a embryo cell line

“…15 Since galectin-1 has been shown to play an important role in both the regulation of apoptosis and cell proliferation, 23,24,34,35 we examined the expression level of galectin-1 in Rat1a cells. Galectin-1, which is constitutively expressed in Rat1a cells expressing ER-FosB or ER-MGMT, is barely detectable in Rat1a(ER-DFosB) cells without estrogen, and is highly induced after estrogen treatment, thus confirming that DFosB does alter the galectin-1 expression even in Rat1a cells.…”

Apoptosis as a target for gene therapy in rheumatoid arthritis

“…The apoptotic effect of Gal-1 depended upon the activation state of T cells and was mediated by engagement of CD43 and CD45, particularly the poly-lactosamine-enriched CD45RO splicing product (Perillo et al 1997). We have recently shown that Gal-1-induced apoptosis is preceded by an early upregulation of the c-Jun proto-oncogene and further activation of the AP-1 transcription factor and is accompanied by a downregulation of Bcl-2 (Rabinovich et al 2000a). Therefore, this protein has been shown to downmodulate exacerbated immune responses and inflammatory processes.…”