Induction of a Caspase-3-like Activity by Calcium in Normal Cytosolic Extracts Triggers Nuclear Apoptosis in a Cell-free System

Juin, Philippe; Pelletier, Maude; Oliver, Lisa; Tremblais, Karine; Grégoire, Marc; Méflah, Khaled; Vallette, François M.

doi:10.1074/jbc.273.28.17559

Cited by 111 publications

(75 citation statements)

References 34 publications

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“…Note that cleavage of CPP-32 is only detected as loss of the pro-enzyme band; the cleavage product is rapidly degraded in the cells and thus is not seen by Western analysis. Similar findings have been reported by other researchers (27,28). (6,10).…”

Section: Modes Of Cell Death Induced In Burkitt's Lymphoma Cells By Vsupporting

confidence: 82%

Oxidative Stress Inhibits Apoptosis in Human Lymphoma Cells

Lee

Shacter

1999

Journal of Biological Chemistry

253

215

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Apoptosis and necrosis are two forms of cell death that are induced under different conditions and that differ in morphological and biochemical features. In this report, we show that, in the presence of oxidative stress, human B lymphoma cells are unable to undergo apoptosis and die instead by a form of necrosis. This was established using the chemotherapy drug VP-16 or the calcium ionophore A23187 to induce apoptosis in Burkitt's lymphoma cell lines and by measuring classical markers of apoptotic death, including cell morphology, annexin V binding, DNA ladder formation, and caspase activation. In the presence of relatively low levels of H 2 O 2 (75-100 M), VP-16 and A23187 were unable to induce apoptosis in these cells. Instead, the cells underwent non-apoptotic cell death with mild cytoplasmic swelling and nuclear shrinkage, similar to the death observed when they were treated with H 2 O 2 alone. We found that H 2 O 2 inhibits apoptosis by depleting the cells of ATP. The effects of H 2 O 2 can be overcome by inhibitors of poly(ADP)-ribosylation, which also preserve cellular ATP levels, and can be mimicked by agents such as oligomycin, which inhibit ATP synthesis. The results show that oxidants can manipulate cell death pathways, diverting the cell away from apoptosis. The potential physiological ramifications of this finding will be discussed.

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Section: Modes Of Cell Death Induced In Burkitt's Lymphoma Cells By Vsupporting

confidence: 82%

Oxidative Stress Inhibits Apoptosis in Human Lymphoma Cells

Lee

Shacter

1999

Journal of Biological Chemistry

253

215

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“…2). This is supported by another study demonstrating that CaCl 2 triggered nuclear apoptosis and increased caspase-3 activity in cell-free systems [176], and one study where caspase-3 activation in vivo was decreased in neurons rescued by treatment with the NMDA receptor antagonist MK-801 after HI [177]. This synergistic enhancement of caspase-3 activation after an excitotoxic insult and calpain activation is a prime example of pathological apoptosis, i.e.…”

Section: Calpains and Caspasessupporting

confidence: 61%

Pathological apoptosis in the developing brain

2007

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More than half of the initially-formed neurons are deleted in certain brain regions during normal development. This process, whereby cells are discretely removed without interfering with the further development of remaining cells, is called programmed cell death (PCD). The term apoptosis is used to describe certain morphological manifestations of PCD. Many of the effectors of this developmental cell death program are highly expressed in the developing brain, making it more susceptible to accidental activation of the death machinery, e.g. following hypoxia-ischemia or irradiation. Recent evidence suggests, however, that activation and regulation of cell death mechanisms under pathological conditions do not exactly mirror physiological, developmentally regulated PCD. It may be argued that the conditions after e.g. ischemia are not even compatible with the execution of PCD as we know it. Under pathological conditions cells are exposed to various stressors, including energy failure, oxidative stress and unbalanced ion fluxes. This results in parallel triggering and potential overshooting of several different cell death pathways, which then interact with one another and result in complex patterns of biochemical manifestations and cellular morphological features. These types of cell death are here called "pathological apoptosis," where classical hallmarks of PCD, like pyknosis, nuclear condensation and caspase-3 activation, are combined with non-PCD features of cell death. Here we review our current knowledge of the mechanisms involved, with special focus on the potential for therapeutic intervention tailored to the needs of the developing brain.

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“…An increase in Ca 2+ concentration has also been reported to lead to activation of caspase-3 [24], while depletion of ER Ca 2+ stores has also been shown to activate PKR and induce phosphorylation of eIF2 [25]. We have also shown Gq-coupled receptor that activates the inositol phosphate pathway and was inhibited by phospholipase C (PLC) inhibitors [26,27].…”

Section: +mentioning

confidence: 58%

Attenuation of skeletal muscle atrophy in cancer cachexia by d-myo-inositol 1,2,6-triphosphate

Russell

Siren²,

Sirén³

et al. 2008

Cancer Chemother Pharmacol

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D-Myo-inositol 1,2,6-triphosphate (alpha trinositol, AT) has been shown to attenuate muscle atrophy in a murine cachexia model through an increase in protein synthesis and a decrease in degradation. The mechanism of this effect has been investigated in murine myotubes using a range of catabolic stimuli, including proteolysis-inducing factor (PIF), angiotensin II (Ang II), lipopolysaccharide, and tumour necrosis factor- / interferon-. At a concentration of 100M AT was found to attenuate both the induction of protein degradation and depression of protein synthesis in response to all stimuli. The effect on protein degradation was accompanied by attenuation of the increased expression and activity of the ubiquitinproteasome pathway. This suggests that AT inhibits a signalling step common to all four agents. This target has been shown to be activation (autophosphorylation) of the dsRNA-dependent protein kinase (PKR) and the subsequent phosphorylation of eukaryotic initiation factor 2 on the -subunit, together with downstream signalling pathways leading to protein degradation. AT also inhibited activation of caspase-3/-8, which is thought to lead to activation of PKR. The mechanism of this effect may be related to the ability of AT to chelate divalent metal ions, since the attenuation of the increased activity of the ubiquitin-proteasome pathway by PIF and Ang II, as well as the depression of protein synthesis by PIF, were reversed by increasing concentrations of Zn 2+. The ability of AT to attenuate muscle atrophy by a range of stimuli suggests that it may be effective in several conditions.

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Induction of a Caspase-3-like Activity by Calcium in Normal Cytosolic Extracts Triggers Nuclear Apoptosis in a Cell-free System

Cited by 111 publications

References 34 publications

Oxidative Stress Inhibits Apoptosis in Human Lymphoma Cells

Oxidative Stress Inhibits Apoptosis in Human Lymphoma Cells

Pathological apoptosis in the developing brain

Attenuation of skeletal muscle atrophy in cancer cachexia by d-myo-inositol 1,2,6-triphosphate

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