title: Spermine triggers the activation of caspase-3 in a cell-free model of apoptosis.
abstract: Polyamines are ubiquitous organic cations required for cell proliferation. However, some evidence suggested that their excessive accumulation can induce apoptosis. We show here that, in a post-nuclear extract from U937 cells, the addition of spermine triggers the death program, represented by cytochrome c exit from mitochondria, the dATP-dependent processing of pro-caspase-3 and the onset of caspase activity. Spermine is more effective than spermidine, whereas putrescine has no effect. Polyamine acetylation abolishes their pro-apoptotic power. These data demonstrate a direct mechanism responsible for polyamine toxicity and also suggest that an excessive elevation of free polyamines could be involved in the transduction of a death signal.
authors.affiliation: Department of Biochemistry G. Moruzzi, University of Bologna, Italy. cstefan@biocfarm.unibo.it
authors.forename: C
authors.initials: C
authors.lastname: Stefanelli
authors.forename: F
authors.initials: F
authors.lastname: Bonavita
authors.forename: I
authors.initials: I
authors.lastname: Stanic'
authors.forename: C
authors.initials: C
authors.lastname: Pignatti
authors.forename: F
authors.initials: F
authors.lastname: Flamigni
authors.forename: C
authors.initials: C
authors.lastname: Guarnieri
authors.forename: C M
authors.initials: CM
authors.lastname: Caldarera
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D002474:Cell-Free System; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D011073:Polyamines / Q000378:metabolism; D051381:Rats; D013096:Spermine / Q000494:pharmacology* / Q000502:physiology*; D013997:Time Factors; D020298:U937 Cells
chemical_list: D011073:Polyamines; D013096:Spermine; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases