Spermine causes caspase activation in leukaemia cells.
Exposure of several leukaemia cell types to the polyamine spermine triggered caspase activation. In HL60 cells, the onset of caspase activity correlated with the accumulation of spermine, and was accompanied by the processing of the caspase-3 precursor and the digestion of the substrate proteins PARP and gelsolin. Spermine also induced the accumulation of cytochrome c in the cytosol. Caspase activation triggered by spermine was not blocked by antioxidants or inhibition of polyamine oxidase. The deregulation of polyamine uptake strongly sensitised the cells to spermine-induced caspase activation. These data show that an excessive intracellular level of spermine triggers caspase activation that is not mediated by oxidative mechanisms, and suggest a model where elevated free cytosolic polyamines may act as transducers of a death message.
Stefanelli
C
C
Department of Biochemistry G. Moruzzi, University of Bologna, Italy. cstefan@biocfarm.unibo.it
Bonavita
F
F
Stanic'
I
I
Mignani
M
M
Facchini
A
A
Pignatti
C
C
Flamigni
F
F
Caldarera
C M
CM
D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D007938:Leukemia / Q000201:enzymology*; D007939:Leukemia L1210; D011073:Polyamines / Q000378:metabolism; D013096:Spermine / Q000494:pharmacology*; D020298:U937 Cells
D011073:Polyamines; D013096:Spermine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases