Caspase Inhibition Selectively Reduces the Apoptotic Component of Oxygen-Glucose Deprivation-Induced Cortical Neuronal Cell Death

Gottron, Frank J.; Ying, Howard S.; Choi, Dennis W.

doi:10.1006/mcne.1997.0618

Cited by 137 publications

(88 citation statements)

References 79 publications

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“…It requires both the PLA 2 activity of subunit B [15] and the ability of the complex to dissociate into their subunits [15,29] . CrTX-induced cytotoxic effects appear to be highly active in cell lines expressing a high density of EGFR [17] , thus suggesting that EGFR, or a receptor function, play a role in targeting.…”

Section: Discussionmentioning

confidence: 99%

“…Effects of autophagy and caspase inhibitors on the cytotoxicity of CrTX It has been reported that LDH leakage not only occurs during necrosis, but also during the process of apoptosis [28,29] . Since 3-MA interferes with the MTT assay, LDH leakage was measured as an index of cell death after co-treatment with CrTX and the autophagic inhibitors 3-MA (10 mmol/L) and NH 4 Cl (10 mmol/L).…”

Section: Vesicular Accumulation Of MDC After Crtx Treatmentmentioning

confidence: 99%

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Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells

Yan

Yang

Qin

et al. 2007

Acta Pharmacologica Sinica

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Aim: To investigate the role of crotoxin (CrTX)‐induced autophagy in the death of MCF‐7 cells, a caspase‐3‐deficient, human breast cancer cell line. Methods: Cultured MCF‐7 cells were treated with various doses of CrTX, a phospholipase A2 (PLA2) isolated from the venom of the South American rattlesnake, Crotalus durissus terrificus. The cytotoxicity of CrTX in the presence and absence of caspase inhibitors was measured with methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) leakage assays. The activation of autophagy was determined with transmission electron microscope and monodansylcadaverin (MDC) labeling. The upregulation of lysosomal enzymes, the release of cyto‐chrome c (cyto‐c), and the nuclear translocation of the apoptosis inducing factor (AIF) were examined by immunoblotting and immunofluorescence. Results: CrTX inhibited the viability of MCF‐7 cells in a dose‐ and time‐dependent manner. CrTX‐activated autophagy was revealed by punctuate MDC labeling, and an increase in the formation of autophagosomes as well as apoptosis, as evidenced by nuclear condensation and fragmentation. The activation of cathepsin B, D, and L, in addition to the release of cytochrome c and the relocation of AIF into nuclei, were observed after CrTX treatment. Autophagy inhibitors 3‐methyladenine (3‐MA), NH4Cl, and the pan‐caspase inhibitor, Z‐Val‐Ala‐Asp‐fluoromethylketone (Z‐Vad‐fmk), attenuated CrTX‐induced cell death. Conclusion: An autophagic mechanism contributes to the apoptosis of MCF‐7 cells induced by CrTX.

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Section: Discussionmentioning

confidence: 99%

Section: Vesicular Accumulation Of MDC After Crtx Treatmentmentioning

confidence: 99%

Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells

Yan

Yang

Qin

et al. 2007

Acta Pharmacologica Sinica

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“…This results in the termination of the overall apoptosis process. Caspase-3-mediated neuronal death has been reported following hypoxic-ischemia in vitro and in vivo (Gottron et al, 1997;Chen et al, 1998;Namura et al, 1998;Fujimura et al, 1998;Sugawara et al, 1999). Wyllie (1980) reported that genomic DNA cleaved into the oligonucleosomal size in the course of apoptosis.…”

Section: Fas Receptormentioning

confidence: 99%

“…Neuronal death by NMDA antagonists reveals a hallmark of apoptosis, such as shrinkage of the cell body, aggregated condensation of nuclear chromatin, and sensitivity to the inhibitors of protein synthesis (Fix et al, 1993;Ikonomidou et al, 1999;Hwang et al, 1999;Takadera et al, 1999). In addition, a prolonged deprivation of oxygen and glucose undergoes slowly-evolving apoptosis through the activation of caspases under the blockade of excitotoxicity Gottron et al, 1997). Accordingly, the combined treatment with a NMDA antagonist and a caspase inhibitor results in synergetic neuroprotection against hypoxic-ischemic injury in vitro and in vivo (Ma et al, 1998;Schulz et al, 1998;Allen et al, 1999;Choi, 2001).…”

Section: Maximization For Prevention Of Hypoxic-ischemic Neuronal Deathmentioning

confidence: 99%

Cellular and Molecular Pathways of Ischemic Neuronal Death

Won¹,

Kim²,

Gwag³

2002

BMB Reports

201

172

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Three routes have been identified triggering neuronal death under physiological and pathological conditions. Excess activation of ionotropic glutamate receptors cause influx and accumulation of Ca 2+ and Na + that result in rapid swelling and subsequent neuronal death within a few hours. The second route is caused by oxidative stress due to accumulation of reactive oxygen and nitrogen species. Apoptosis or programmed cell death that often occurs during developmental process has been coined as additional route to pathological neuronal death in the mature nervous system. Evidence is being accumulated that excitotoxicity, oxidative stress, and apoptosis propagate through distinctive and mutually exclusive signal transduction pathway and contribute to neuronal loss following hypoxic-ischemic brain injury. Thus, the therapeutic intervention of hypoxic-ischemic neuronal injury should be aimed to prevent excitotoxicity, oxidative stress, and apoptosis in a concerted way.

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“…The simplistic notion that all neurodegenerative diseases are diseases of enhanced apoptosis is unlikely to be entirely correct. For example, death of cortical neuronal cells from serum withdrawal is dependent on an apoptotic program, but excitotoxic death induced in the same cells by kainate has a major necrotic component (Gottron et al, 1997). Thus, the details of the putative relationship between developmental and degenerative neuronal cell death remain unknown.…”

mentioning

confidence: 99%

Caspases on the brain

Troy

Salvesen

2002

J of Neuroscience Research

106

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The basic mechanisms that underlie neurodegenerative diseases are unknown. Loss of function of specific regions of the brain is due to incapacitation of cells that constitute those regions. Cells can simply stop functioning normally (neurons may cease to transmit signals), or they may die. There is now evidence that the pathology of several neurodegenerative diseases is due to inappropriate apoptosis. This being the case, an understanding of the mediators of apoptosis, their identities, and their role in orchestrating death would be a vital step toward remedying the diseases. The central components of apoptotic pathways, proteases of the caspase family, are present in latent forms in all nucleated cells. Their activity is balanced by specific activation and inactivation events, and the molecular and biochemical controls have been well established in vitro and in model transformed cell lines. In this Mini‐Review, we consider the current status of the basic control mechanisms and how these may be subverted during neurodegeneration. © 2002 Wiley‐Liss, Inc.

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Caspase Inhibition Selectively Reduces the Apoptotic Component of Oxygen-Glucose Deprivation-Induced Cortical Neuronal Cell Death

Cited by 137 publications

References 79 publications

Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells

Autophagy is involved in cytotoxic effects of crotoxin in human breast cancer cell line MCF-7 cells

Cellular and Molecular Pathways of Ischemic Neuronal Death

Caspases on the brain

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