Spermine causes caspase activation in leukaemia cells

Stefanelli, Claudio; Bonavita, Francesca; Stanic, Ivana; Mignani, Monica; Facchini, Angelo; Pignatti, Carla; Flamigni, Flavio; Caldarera, Claudio Marcello

doi:10.1016/s0014-5793(98)01239-3

Cited by 97 publications

(68 citation statements)

References 37 publications

(58 reference statements)

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“…Consistent with the role of PAs as positive regulators of cell growth, these compounds protect cells from apoptosis and their overproduction has been linked to cell overproliferation and malignant development in animal cells (Wallace et al, 2003). On the other hand, either the increase or the decrease of physiological levels of PAs, induce the execution of the programmed cell death (PCD) syndrome (Seiler and Raul, 2005) either by caspase activation (Stefanelli et al, 1998) or cytochrome c release from mitocondria (Stefanelli et al, 2000), revealing PAs as bivalent regulators of cellular functions.…”

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confidence: 80%

Perturbation of Polyamine Catabolism Can Strongly Affect Root Development and Xylem Differentiation

et al. 2011

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Spermidine (Spd) treatment inhibited root cell elongation, promoted deposition of phenolics in cell walls of rhizodermis, xylem elements, and vascular parenchyma, and resulted in a higher number of cells resting in G 1 and G 2 phases in the maize (Zea mays) primary root apex. Furthermore, Spd treatment induced nuclear condensation and DNA fragmentation as well as precocious differentiation and cell death in both early metaxylem and late metaxylem precursors. Treatment with either N-prenylagmatine, a selective inhibitor of polyamine oxidase (PAO) enzyme activity, or N,N 1 -dimethylthiourea, a hydrogen peroxide (H 2 O 2 ) scavenger, reverted Spd-induced autofluorescence intensification, DNA fragmentation, inhibition of root cell elongation, as well as reduction of percentage of nuclei in S phase. Transmission electron microscopy showed that N-prenylagmatine inhibited the differentiation of the secondary wall of early and late metaxylem elements, and xylem parenchymal cells. Moreover, although root growth and xylem differentiation in antisense PAO tobacco (Nicotiana tabacum) plants were unaltered, overexpression of maize PAO (SZmPAO) as well as down-regulation of the gene encoding S-adenosyl-L-methionine decarboxylase via RNAi in tobacco plants promoted vascular cell differentiation and induced programmed cell death in root cap cells. Furthermore, following Spd treatment in maize and ZmPAO overexpression in tobacco, the in vivo H 2 O 2 production was enhanced in xylem tissues. Overall, our results suggest that, after Spd supply or PAO overexpression, H 2 O 2 derived from polyamine catabolism behaves as a signal for secondary wall deposition and for induction of developmental programmed cell death.

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confidence: 80%

Perturbation of Polyamine Catabolism Can Strongly Affect Root Development and Xylem Differentiation

et al. 2011

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“…We have described here a cardiac cell-free model of apoptosis : caspase activity in cytosol of embryonal cardiomyocytes is triggered by the cytochrome c released from mitochondria by spermine. The described cell-free model can directly explain the toxicity of an excessively high level of intracellular spermine [11,44]. In fact, spermine and spermidine are present in high amounts within the cells, but are acknowledged to be almost totally bound to anionic structures, leaving only low concentrations of free polyamines [45].…”

Section: Discussionmentioning

confidence: 99%

“…Even if polyamines are necessary for growth processes, their excessive accumulation triggers apoptosis [7][8][9][10][11]. Activation of caspases represents a fundamental point in apoptosis [12] and mitochondria play a central role in this process [13], since the release of an apoptogenic factor, like cytochrome c, into the cytosol is a crucial step for caspase activation [14].…”

Section: Introductionmentioning

confidence: 99%

“…However, cytochrome c leakage in apoptotic cells is evident before mitochondria damage [18]. Spermine causes the leakage of cytochrome c into the cytosol both in whole cells [11] and in cell extracts containing mitochondria along with cytosol [19]. In order to study the mechanism of spermine action, we tested the hypothesis that spermine could directly affect the translocation of cytochrome c. The present paper reports that polyamines can Abbreviations used : CEHC, chick embryo heart cells ; CsA, cyclosporin A ; MIB, mitochondria incubation buffer ; MPT, mitochondrial permeability transition ; P/O ratio, ratio of ATP synthesized/O 2 consumed.…”

Section: Introductionmentioning

confidence: 99%

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Polyamines directly induce release of cytochrome c from heart mitochondria

Stefanelli

Stanic

Zini

et al. 2000

Biochemical Journal

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Cytochrome c release from mitochondria to the cytosol represents a critical step in apoptosis, correlated to the activation of the caspase cascade. In this report, we show that addition of micromolar concentrations of polyamines to isolated rat heart mitochondria induces the release of cytochrome c. Spermine, which is effective at concentrations of 10-100 μM, is more potent than spermidine, whereas putrescine has no effect up to 1 mM. The release of cytochrome c caused by spermine is a rapid, saturable and selective process that is independent of mitochondria damage. Spermine, unlike polylysine, is able to release a discrete amount of cytochrome c from intact, functional mitochondria. The cytochrome c-releasing power of spermine is not affected by cyclosporin A, differently from the effect of permeability transition inducers. In a cardiac cell-free model of apoptosis, the latent caspase activity of cytosolic extracts from cardiomyocytes could be activated by cytochrome c released from spermine-treated heart mitochondria. These data indicate a novel mechanism of cytochrome c release from the mitochondrion, and suggest that prolonged and sustained elevation of polyamines, characteristic of some pathologies such as heart hypertrophy, could be involved in the development of apoptosis.

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“…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.…”

Section: Corolla Of Excised Flowersmentioning

confidence: 99%

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

et al. 2002

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Corolla life span of undetached flowers of Nicotiana tabacum was divided into stages from the closed corolla (stage 1) through anthesis (stage 5) to death (stage 9). Senescence began around stage 6 in the proximal part, concomitantly with DNA laddering. Nuclear blebbing, DNA laddering, cell wall modification, decline in protein, water, pigment content and membrane integrity were observed during senescence and PCD. Transglutaminase activity was measured as mono-and bis-derivatives of putrescine (mono-PU; bis-PU) and bis-derivatives of spermidine (bis-SD). Bis-derivatives decreased with the progression of senescence, while mono-PU increased during early senescence; derivatives were present in different amounts in the proximal and distal parts of the corolla. In excised flowers, exogenous spermine delayed senescence and PCD, and caused an increase in free and acid-soluble conjugated PA levels. Bis-PU was the most abundant PA-derivative before DNA laddering stage; thereafter, bis-PU generally decreased and mono-PU became the most abundant derivative.

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Spermine causes caspase activation in leukaemia cells

Cited by 97 publications

References 37 publications

Perturbation of Polyamine Catabolism Can Strongly Affect Root Development and Xylem Differentiation

Perturbation of Polyamine Catabolism Can Strongly Affect Root Development and Xylem Differentiation

Polyamines directly induce release of cytochrome c from heart mitochondria

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

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