The mechanism of apoptosis induced by human galectin-1, a mammalian beta-galactoside-binding
protein with a remarkable cytotoxic effect on activated peripheral T cells and tumor
T cell lines has been extensively investigated in this study. Here we first show that
galectin-1 initiate the acid sphingomyelinase mediated release of ceramide and this
event is critical in the further steps. Elevation of ceramide level coincides with
exposure of phosphatidylserine on the outer cell membrane. The downstream events,
decrease of Bcl-2 protein amount, depolarization of the mitochondria and activation
of the caspase 9 and caspase 3 depend on production of ceramide. All downstream steps,
including production of ceramide, require the generation of membrane rafts and the
presence of two tyrosine kinases, p56(lck) and ZAP70. Based on our findings we suggest
a model of the mechanism of galectin-1 triggered cell death.
