Cyclosporin A inhibits caspase-independent death of NGF-deprived sympathetic neurons

Opening of the permeability transition pore (PTP) has been implicated as an important mitochondrial event that occurs during apoptosis. We examined the role of the PTP in the well-characterized cell death of rat sympathetic neurons deprived of nerve growth factor (NGF) in vitro. Removal of NGF causes these neurons to undergo either a classic apoptotic cell death or, when treated with a broad-spectrum caspase inhibitor such as boc-aspartyl(OMe)-fluoromethylketone (BAF), a delayed, nonapoptotic cell death. The PTP inhibitor, cyclosporin A (CsA), blocked commitment-to-die in the presence of BAF, as defined by the ability of NGF readdition to rescue cells, but had little effect on commitment-to-die in the absence of BAF. CsA did not have trophic effects on BAF-saved cells, but did block the decrease in mitochondrial membrane potential. These data suggest that PTP opening is a critical event in caspase-independent, nonapoptotic (but not caspase-dependent, apoptotic) death of NGF-deprived rat sympathetic neurons.

• Publication year

  2002

• Venue

  Journal of Cell Biology

• Publication date

  2002-05-28

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1083/jcb.200112130PMID 12021257PMCID 2173417
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• Mitochondrial Depolarization Accompanies Cytochrome cRelease During Apoptosis in PC6 Cells*

  1999cited by this paper
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  1999cited by this paper
• Proteases to die for.

  1998cited by this paper
• Superoxide in Apoptosis

  1998cited by this paper
• Mitochondrial cytochrome c release in apoptosis occurs upstream of DEVD‐specific caspase activation and independently of mitochondrial transmembrane depolarization

  1998cited by this paper
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  1998cited by this paper
• Blocking Cytochrome c Activity within Intact Neurons Inhibits Apoptosis

  1998cited by this paper
• Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis.

  1998cited by this paper
• Attenuation of ischemia/reperfusion injury in rats by a caspase inhibitor.

  1998cited by this paper
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  1998cited by this paper
• Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade.

  1997cited by this paper
• Inhibition of interleukin 1beta converting enzyme family proteases reduces ischemic and excitotoxic neuronal damage.

  1997cited by this paper
• Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria.

  1997cited by this paper
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  1996cited by this paper
• Mitochondrial permeability transition is a central coordinating event of apoptosis

  1996cited by this paper
• BAX is required for neuronal death after trophic factor deprivation and during development.

  1996cited by this paper
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  1996cited by this paper
• Genetic and metabolic status of NGF-deprived sympathetic neurons saved by an inhibitor of ICE family proteases

  1996cited by this paper
• Chronic depolarization prevents programmed death of sympathetic neurons in vitro but does not support growth: requirement for Ca2+ influx but not Trk activation

  1995cited by this paper
• Contribution of the mitochondrial permeability transition to lethal injury after exposure of hepatocytes to t-butylhydroperoxide.

  1995cited by this paper
• Characterization of apoptosis in cultured rat sympathetic neurons after nerve growth factor withdrawal

  1994cited by this paper
• Temporal analysis of events associated with programmed cell death (apoptosis) of sympathetic neurons deprived of nerve growth factor

  1993cited by this paper
• On the involvement of a cyclosporin A sensitive mitochondrial pore in myocardial reperfusion injury.

  1993cited by this paper
• cAMP analogs promote survival and neurite outgrowth in cultures of rat sympathetic and sensory neurons independently of nerve growth factor.

  1988cited by this paper
• Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation

  1988influential reference
• FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro.

  1987cited by this paper
• Evidence for the presence of a reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria.

  1987cited by this paper
• FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics.

  1987cited by this paper
• The Ca2+-induced membrane transition in mitochondria. III. Transitional Ca2+ release.

  1979cited by this paper
• The Ca2+-induced membrane transition in mitochondria. I. The protective mechanisms.

  1979cited by this paper
• Apoptosis: A Basic Biological Phenomenon with Wide-ranging Implications in Tissue Kinetics

  1972cited by this paper

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  2020cites this paper
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  2019cites this paper
• Chlorogenic acid prevents paraquat-induced apoptosis via Sirt1-mediated regulation of redox and mitochondrial function

  2019cites this paper
• Apoptotic cell death regulation in neurons

  2019cites this paper
• Mdivi-1 alleviates blood-brain barrier disruption and cell death in experimental traumatic brain injury by mitigating autophagy dysfunction and mitophagy activation.

  2018cites this paper
• Functional analysis of glyco-molecules that bind with influenza virus.

  2016cites this paper
• Role of sulfatide in influenza A virus replication.

  2015cites this paper
• Poloxamer 188 Attenuates Cerebral Hypoxia/Ischemia Injury in Parallel with Preventing Mitochondrial Membrane Permeabilization and Autophagic Activation

  2015cites this paper
• N-Acetyl-Serotonin Offers Neuroprotection through Inhibiting Mitochondrial Death Pathways and Autophagic Activation in Experimental Models of Ischemic Injury

  2014cites this paper
• The E3 ligase PARC mediates the degradation of cytosolic cytochrome c to promote survival in neurons and cancer cells

  2014cites this paper
• Mitochondria-derived reactive oxygen species mediate caspase-dependent and -independent neuronal deaths.

  2014influential citation
• Sulfatide Regulates Caspase-3-Independent Apoptosis of Influenza A Virus through Viral PB1-F2 Protein

  2013influential citation
• The transcription factor Pax6 regulates survival of dopaminergic olfactory bulb neurons via crystallin αA.

  2010cites this paper
• Mitochondrial membrane potential disruption pattern in human sperm.

  2009cites this paper
• Cytoplasmic Inclusions of Htt Exon1 Containing an Expanded Polyglutamine Tract Suppress Execution of Apoptosis in Sympathetic Neurons

  2008cites this paper
• Nortriptyline Protects Mitochondria and Reduces Cerebral Ischemia/Hypoxia Injury

  2008cites this paper
• Modeling of the role of a Bax-activation switch in the mitochondrial apoptosis decision.

  2007cites this paper
• Cell death in rat cerebellar granule neurons induced by hydrogen peroxide in vitro: mechanisms and protection by adenosine receptor ligands.

  2007cites this paper
• Type 2 transglutaminase differentially modulates striatal cell death in the presence of wild type or mutant huntingtin

  2007cites this paper
• Restricting Apoptosis for Postmitotic Cell Survival and its Relevance to Cancer

  2006cites this paper
• Oxidative stress and the viability of osteoblasts and cerebellar granule neurones.

  2006cites this paper
• Gold(III) Porphyrin 1a Induced Apoptosis by Mitochondrial Death Pathways Related to Reactive Oxygen Species

  2005cites this paper
• Enhancement of cyanide-induced mitochondrial dysfunction and cortical cell necrosis by uncoupling protein-2.

  2005cites this paper
• GoldIII porphyrin 1a induced apoptosis by mitochondrial death pathways related to reactive oxygen species.

  2005cites this paper
• Caspase-Dependent and -Independent Neuronal Death: Two Distinct Pathways to Neuronal Injury

  2005cites this paper
• Cyclosporine protects against ischemia/reperfusion injury in rat kidneys.

  2005cites this paper
• Death Pathways Related to Reactive Oxygen Species Gold ( III ) Porphyrin 1 a Induced Apoptosis by Mitochondrial

  2005cites this paper
• ‘Men are but worms:’⋆ neuronal cell death in C. elegans and vertebrates

  2004cites this paper
• Caspase-independent component of retinal ganglion cell death, in vitro.

  2004cites this paper
• Role of AIF in caspase-dependent and caspase-independent cell death

  2004cites this paper
• Cyclosporin A enhances colchicine‐induced apoptosis in rat cerebellar granule neurons

  2004cites this paper
• Striatal cells from mutant huntingtin knock-in mice are selectively vulnerable to mitochondrial complex II inhibitor-induced cell death through a non-apoptotic pathway.

  2004cites this paper
• Control of mitochondrial integrity by Bcl-2 family members and caspase-independent cell death.

  2004cites this paper
• Inhibition of caspase-mediated PARP-1 cleavage results in increased necrosis in isolated islets of Langerhans

  2004cites this paper
• Dynamic analysis of apoptosis in primary cortical neurons by fixed- and real-time cytofluorometry

  2004cites this paper
• Histologic Features in Primary Cutaneous Squamous Cell Carcinomas in Immunocompromised Patients Focusing on Organ Transplant Patients

  2004cites this paper
• Apoptosis in the myocardium: much is still expected

  2003cites this paper
• Aluminum disrupts the pro-inflammatory cytokine/neurotrophin balance in primary brain rotation-mediated aggregate cultures: possible role in neurodegeneration.

  2003cites this paper
• Activated/effector CD4+ T cells exacerbate acute damage in the central nervous system following traumatic injury.

  2003cites this paper
• The Effects of Oxidative Stress on Mitochondrial Transmembrane Potential in Retinal Ganglion Cells

  2003cites this paper
• Cell-type-specific opening of the retinal ganglion cell mitochondrial permeability transition pore.

  2003influential citation
• Mechanisms of Caspase-Independent Neuronal Death: Energy Depletion and Free Radical Generation

  2003cites this paper
• PLA2 activity is required for nuclear shrinkage in caspase-independent cell death

  2003cites this paper
• Alternating metabolic pathways in NGF-deprived sympathetic neurons affect caspase-independent death

  2003influential citation
• Outer mitochondrial membrane permeabilization during apoptosis triggers caspase-independent mitochondrial and caspase-dependent plasma membrane potential depolarization: a single-cell analysis

  2003cites this paper
• Reactive Oxygen Species Generation and Mitochondrial Dysfunction in the Apoptotic Response to Bortezomib, a Novel Proteasome Inhibitor, in Human H460 Non-small Cell Lung Cancer Cells*

  2003cites this paper
• The role of mitochondria in nitric oxide-mediated thymocyte apoptosis.

  2003cites this paper
• Aluminum neurotoxicity involves oxidative stress, inflammation and apoptosis : implications for neurodegeneration

  2002cites this paper