Mediation of Poly(ADP-Ribose) Polymerase-1-Dependent Cell Death by Apoptosis-Inducing Factor

Yu, Sebastian; Wang, Hongmin; Poitras, Marc F.; Coombs, Carmen; Bowers, William J.; Federoff, Howard J.; Poirier, Guy G.; Dawson, Ted M.; Dawson, Valina L.

doi:10.1126/science.1072221

Cited by 1,654 publications

(1,560 citation statements)

References 27 publications

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“…Another possibility is that AIF is not the alone effector of A3D8-induced cell death. Indeed, the phenotype of cell death described here was not identical to the previously identified AIF-induced cell death involving delayed cytochrome c release and subsequent caspase cascade (Susin et al, 1999;Yu et al, 2002). Thus, it is possible that death effectors other than AIF contribute to the caspase-independent cell death induced by A3D8.…”

Section: Discussioncontrasting

confidence: 73%

“…Recent observations indicated that AIF may be a key molecule in PARP-1-mediated caspase-independent cell death (Yu et al, 2002;Hong et al, 2004). Although the mechanism of PARP-1-mediated release of AIF remains elusive, it appears to be involved in apoptotic forms of cell death.…”

Section: Discussionmentioning

confidence: 99%

“…Poly (ADP-ribose) polymerase-1 is involved in cell death induced by A3D8 and in apoptosis-inducing factor nuclear translocation Recent studies indicate that AIF is a key mediator of caspase-independent cell death mediated by PARP-1 activation (Yu et al, 2002;Hong et al, 2004). We therefore tested the effects of pharmacological PARP-1 inhibitor 1,5-isoquinolinediol on A3D8-treated HEL cells.…”

Section: Apoptosis-inducing Factor Translocates To the Nucleus And Mementioning

confidence: 99%

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CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

et al. 2006

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Ligation of the cell surface molecule CD44 by anti-CD44 monoclonal antibodies (mAbs) has been shown to induce cell differentiation, cell growth inhibition and in some cases, apoptosis in myeloid leukemic cells. We report, herein, that exposure of human erythroleukemic HEL cells to the anti-CD44 mAb A3D8 resulted in cell growth inhibition followed by caspase-independent apoptosis-like cell death. This process was associated with the disruption of mitochondrial membrane potential (DWm), the mitochondrial release of apoptosis-inducing factor (AIF), but not of cytochrome c, and the nuclear translocation of AIF. All these effects including cell death, loss of mitochondrial DWm and AIF release were blocked by pretreatment with the poly (ADP-ribose) polymerase inhibitor isoquinoline. A significant protection against cell death was also observed by using small interfering RNA for AIF. Moreover, we show that calpain protease was activated before the appearance of apoptosis, and that calpain inhibitors or transfection of calpain-siRNA decrease A3D8-induced cell death, and block AIF release. These data suggest that CD44 ligation triggers a novel caspaseindependent cell death pathway via calpain-dependent AIF release in erythroleukemic HEL cells.

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Section: Discussioncontrasting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Apoptosis-inducing Factor Translocates To the Nucleus And Mementioning

confidence: 99%

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CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

et al. 2006

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“…Apart from the apoptotic role of AIF following its release and translocation to the nucleus [3,[139][140][141][142], AIF also has a physiological Fig. 4 During excitotoxicity, elongated mitochondria along the neurite and at the synapse can buffer Ca 2+ more effectively than fragmented mitochondria.…”

Section: Mitochondrial Cristae Structure and Cell Death: Demolition Fmentioning

confidence: 99%

Mitochondrial dynamics in the regulation of neuronal cell death

2007

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Mitochondria undergo continuous fission and fusion events in physiological situations. Fragmentation of mitochondria during cell death has been shown to play a key role in cell death progression, including release of the mitochondrial apoptotic proteins. Ultrastructural changes in mitochondria, such as cristae remodeling, is also involved in cell death initiation. Here, we emphasize the important role of mitochondrial fission/fusion machinery in neuronal cell death. Unlike many other cell types such as immortalized cell lines, neurons are distinct morphologically and functionally. We will discuss how this uniqueness presents special challenges in the cellular response to neurotoxic stresses, and how this affects the mitochondrial dynamics in the regulation of cell death in neurons.

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“…Taking advantage of a procedure involving the preferential conformation of cationic dye in mitochondria (alive cells) or in cytoplasm (apoptotic cells), we then examined the mechanism that underlies the marked reduction of cells number and the modifications of cell morphology caused by ABT-737. TFK-1 cells were treated with 30 µM ZOL and 10 µM ABT-737 alone or in combination (Fig.4A), while EGI-1 cells were treated with 15 µM ZOL and 3 µM ABT-737 alone or in combination (Fig.4B) Recently, a specific PARP-1 mediated caspaseindependent pathway of cell death leading to the translocation of the mitochondrial apoptosisinducing factor (AIF) via cytoplasm to the nucleus has been described [31]. To analyze the discrepancy between earlier PARP-1 activation in comparison to caspase cleavage in our cell lines, we then verified AIF releasing in the cytoplasm following ABT737 and/or ZOL exposure.…”

Section: Mitochondrial Depolarization Assessmentmentioning

confidence: 99%

The BH3-mimetic ABT-737 targets the apoptotic machinery in cholangiocarcinoma cell lines resulting in synergistic interactions with zoledronic acid

Romani

Desenzani

Morganti

et al. 2010

Cancer Chemother Pharmacol

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Purpose: In TFK-1 and EGI-1 cholangiocarcinoma cell lines zoledronic acid (ZOL) determines a S-phase block without apoptosis. Here we investigated the occurrence of apoptosis stigmata when ZOL is associated to the BH3-mimetic ABT-737. Methods:In EGI-1 and TFK-1 cholangiocarcinoma cell lines untreated or treated with ABT-737 alone or in combination with ZOL, the pro-survival proteins pattern (BCL-2, BCL-XL, MCL-1, HSP72, HSP27) was investigated by biochemical criteria along with the occurrence of mitochondrial damage evaluated by cytofluorimetric analysis using a cationic dye.Results: ABT-737 induced growth inhibition and significantly affected the colony-forming ability of both EGI-1 and TFK-1 cells. However, activated PARP-1 or/and caspase-3 cleavage (apoptosis markers) were detected only at the highest ABT-737 concentrations used. Combined treatment showed synergistic effect by converting the predominant cytostatic effect of ZOL into a cytotoxic one as shown by striking increment of mitochondrial-harmed cells along with PARP-1 activation and caspase-3 cleavage. Conclusion:The lacking of apoptosis following ZOL treatment in these cholangiocarcinoma cell lines appears to be multifactorial and could be ascribed to the large constitutive expression of prosurvival proteins. The efficacy of ZOL treatment requires a concomitant unleashing of apoptosis by using a selective BH3-mimetic as ABT-737. The rational targeting of specific components of the apoptotic pathway may appear a useful approach to improve the treatment of refractory or relapsed cholangiocarcinoma. Combined treatment could be further explored in vivo tumor model of cholangiocarcinoma

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Mediation of Poly(ADP-Ribose) Polymerase-1-Dependent Cell Death by Apoptosis-Inducing Factor

Cited by 1,654 publications

References 27 publications

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

CD44 ligation induces caspase-independent cell death via a novel calpain/AIF pathway in human erythroleukemia cells

Mitochondrial dynamics in the regulation of neuronal cell death

The BH3-mimetic ABT-737 targets the apoptotic machinery in cholangiocarcinoma cell lines resulting in synergistic interactions with zoledronic acid

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