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.z 1999 Federation of European Biochemical Societies.

Polyamine-mediated Apoptosis of Alveolar Macrophages during Pneumocystis Pneumonia

“…This apoptosis is also characterized by mitochondrial damage and activation of caspase-9 (31,66), similar to what is seen in alveolar macrophages during Pcp. Polyamines can stimulate apoptosis of cells directly (32,34,35) or through the generation of ROS (67,68). Data of the current study suggest that polyamines induce apoptosis of alveolar macrophages via ROS during Pcp (Table 6).…”

“…This apoptosis is mediated through a structural protein, PorB, in the outer bacterial cell wall (25). It is believed that PorB forms a pore structure on the cell membrane of the target cell, with subsequent rises in cytosolic Ca 2ϩ and activation of caspase-3 (35,59). Mycobacterium tuberculosis also induces apoptosis in host macrophages (24,60).…”

“…The primary polyamines putrescine, spermine, and spermidine are all implicated in initiation of apoptosis, but spermine and N 1 -acetylspermine are more often involved in the direct toxic effects of polyamines on the membrane potential of the mitochondria (32,34). Spermine can directly activate caspase-3 in macrophage-like cell lines (35). Polyamines can affect the activity of transcription factors such as NF-B (36) and AP-1 (37), which in turn control the transcription of many other genes.…”

Transglutaminase activity during senescence and programmed cell death in the corolla of tobacco (Nicotiana tabacum) flowers

“…69 SM also caused cytochrome c exit from mitochondria and caspase activation in leukaemia cells and in a cell free system. 70,71 In these systems, a 2 ± 4-fold accumulation of free cytosolic PAs was responsible for the activation of the death programme. 69,71 In senescent Nicotiana corollas supplied with SM, free PAs increased to a similar extent; however, differently from animal cells, plants can buffer against excess PAs by conjugating them to low molecular weight molecules (TCA-soluble conjugates) and compartment them in the vacuole.…”

“…70,71 In these systems, a 2 ± 4-fold accumulation of free cytosolic PAs was responsible for the activation of the death programme. 69,71 In senescent Nicotiana corollas supplied with SM, free PAs increased to a similar extent; however, differently from animal cells, plants can buffer against excess PAs by conjugating them to low molecular weight molecules (TCA-soluble conjugates) and compartment them in the vacuole. 72 Thus, the different effects of free PAs on apoptosis could also depend on their real concentration in the cytoplasm and organelles.…”