Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling

Hong, Suk Jin; Dawson, Ted M.; Dawson, Valina L.

doi:10.1016/j.tips.2004.03.005

Cited by 419 publications

(316 citation statements)

References 53 publications

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“…Second, PARP-1's importance in ischemic neuronal death is also sexually dimorphic. Poly-ADP ribose polymerase activation has been widely studied as a potentially deleterious response to nitrosative or oxidative DNA damage subsequent to ischemic insult (Hong et al, 2004;Virag and Szabo, 2002;Virag et al, 2003;Ha and Snyder, 2000;Eliasson et al, 1997;Mandir et al, 2000;Pieper et al, 1999;Endres et al, 1997Endres et al, , 1998. In contrast to the male where stroke-induced PARP-1 activation promotes bioenergetic failure, proapoptotic signaling, mitochondrial dysfunction, and cell death, PARP-1 is utilized to restrict tissue damage in the female.…”

Section: Discussionmentioning

confidence: 99%

“…One well-studied mechanism of neuronal cell death in cerebral ischemia and trauma occurs by a serially linked set of events: overstimulation of neuronal nitric oxide synthase (nNOS) leading to toxic local elaboration of nitric oxide (NO), subsequent peroxynitrite formation and nitrosative DNA damage, activation of the DNA repair enzyme poly ADP ribose polymerase-1 (PARP-1), and PARP-1-induced mobilization of proapoptotic molecules such as apoptosis inducing factor (AIF) (Endres et al, 1998;Yu et al, 2002Yu et al, , 2003Du et al, 2003;Hong et al, 2004;Plesnila et al, 2004). Key evidence in establishing NO toxicity/PARP-1 activation as a major cytotoxic mechanism has accumulated from exclusively male animals with targeted deletions of nNOS (nNOSÀ/À) or PARP (PARPÀ/À).…”

Section: Introductionmentioning

confidence: 99%

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Ischemic Nitric Oxide and Poly (ADP-Ribose) Polymerase-1 in Cerebral Ischemia: Male Toxicity, Female Protection

McCullough

Zeng

Blizzard

et al. 2005

J Cereb Blood Flow Metab

293

324

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It is well established that tissue damage and functional outcome after experimental or clinical stroke are shaped by biologic sex. We investigated the novel hypothesis that ischemic cell death from neuronally derived nitric oxide (NO) or poly-ADP ribose polymerase (PARP-1) activation is sexually dimorphic and that interruption of these molecular death pathways benefits only the male brain. Female neuronal nitric oxide synthase (nNOS) knockout (nNOSÀ/À) mice exhibited exacerbated histological injury after middle cerebral artery occlusion (MCAO) relative to wild-type (WT) females, unlike the protection observed in male nNOSÀ/À littermates. Similarly, treatment with the nNOS inhibitor (7-nitroindozole, 25 mg/kg) increased infarction in female C57Bl6 WT mice, but protected male mice. The mechanism for this sexually specific response is not mediated through changes in protein expression of endothelial NOS or inducible NOS, or differences in intraischemic cerebral blood flow. Unlike male PARP-1 knockouts (PARP1À/À), female PARP1À/À littermates sustained grossly increased ischemic damage relative to sex-matched WT mice. Treatment with a PARP inhibitor (PJ-34, 10 mg/kg) resulted in identical results. Loss of PARP-1 resulted in reversal of the neuroprotective activity by the female sex steroid, 17b estradiol. These data suggest that the previously described cell death pathways involving NO and PARP ischemic neurotoxicity may be operant solely in male brain and that the integrity of nNO/PARP-1 signaling is paradoxically protective in the female.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ischemic Nitric Oxide and Poly (ADP-Ribose) Polymerase-1 in Cerebral Ischemia: Male Toxicity, Female Protection

McCullough

Zeng

Blizzard

et al. 2005

J Cereb Blood Flow Metab

293

324

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“…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%

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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“…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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Nuclear and mitochondrial conversations in cell death: PARP-1 and AIF signaling

Cited by 419 publications

References 53 publications

Ischemic Nitric Oxide and Poly (ADP-Ribose) Polymerase-1 in Cerebral Ischemia: Male Toxicity, Female Protection

Ischemic Nitric Oxide and Poly (ADP-Ribose) Polymerase-1 in Cerebral Ischemia: Male Toxicity, Female Protection

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

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