SPERMINE CAUSES CASPASE ACTIVATION IN LEUKEMIA-CELLS

Exposure of several leukaemia cell types to the polyamine spermine tri ggered caspase activation. In HL60 cells, the onset of caspase activit y correlated with the accumulation of spermine, and was accompanied by the processing of the caspase-3 precursor and the digestion of the su bstrate proteins PARP and gelsolin, Spermine also induced the accumula tion of cytochrome c in the cytosol. Caspase activation triggered by s permine was not blocked by antioxidants or inhibition of polyamine oxi dase. The deregulation of polyamine uptake strongly sensitised the cel ls to spermine-induced caspase activation, These data show that an exc essive intracellular level of spermine triggers caspase activation tha t is not mediated by oxidative mechanisms, and suggest a model where e levated free cytosolic polyamines may act as transducers of a death me ssage. (C) 1998 Federation of European Biochemical Societies.