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Oxidative stress, mitochondrial permeability transition and activation of caspases in calcium ionophore A23187-induced death of cultured striatal neurons

Petersén, Åsa LU ; Castilho, Roger F. ; Hansson, Oskar LU ; Wieloch, Tadeusz LU and Brundin, Patrik LU (2000) In Brain Research 857(1-2). p.20-29
Abstract

Disruption of intracellular calcium homeostasis is thought to play a role in neurodegenerative disorders such as Huntington's disease (HD). To study different aspects of putative pathogenic mechanisms in HD, we aimed to establish an in vitro model of calcium-induced toxicity in striatal neurons. The calcium ionophore A23187 induced a concentration- and time-dependent cell death in cultures of embryonic striatal neurons, causing both apoptosis and necrosis. Cell death was significantly reduced by the cell-permeant antioxidant manganese(III)tetrakis(4-benzoic acid) porphyrin (MnTBAP). Cyclosporin A and its analogue N-MeVal-4-cyclosporin also reduced the incidence of cell death, suggesting the participation of mitochondrial permeability... (More)

Disruption of intracellular calcium homeostasis is thought to play a role in neurodegenerative disorders such as Huntington's disease (HD). To study different aspects of putative pathogenic mechanisms in HD, we aimed to establish an in vitro model of calcium-induced toxicity in striatal neurons. The calcium ionophore A23187 induced a concentration- and time-dependent cell death in cultures of embryonic striatal neurons, causing both apoptosis and necrosis. Cell death was significantly reduced by the cell-permeant antioxidant manganese(III)tetrakis(4-benzoic acid) porphyrin (MnTBAP). Cyclosporin A and its analogue N-MeVal-4-cyclosporin also reduced the incidence of cell death, suggesting the participation of mitochondrial permeability transition in this process. Furthermore, addition of either of two types of caspase inhibitors, Ac-YVAD-CHO (acetyl-Tyr-Val-Ala-Asp-aldehyde) and Ac-DEVD-CHO (acetyl-Asp-Glu-Val-Asp-aldehyde), to the striatal cells blocked A23187-induced striatal cell death in a concentration-dependent manner. These results suggest that oxidative stress, opening of the mitochondrial permeability transition pore and activation of caspases are important steps in A23187-induced cell death. Copyright (C) 2000 Elsevier Science B.V.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Apoptosis, Calcium, Cell death, Huntington's disease, Mitochondria, Striatal neuron
in
Brain Research
volume
857
issue
1-2
pages
10 pages
publisher
Elsevier
external identifiers
  • pmid:10700549
  • scopus:0033975779
ISSN
0006-8993
DOI
10.1016/S0006-8993(99)02320-3
language
English
LU publication?
yes
id
38d6f310-a41a-4261-92d3-09d3890fd217
date added to LUP
2019-06-13 16:40:02
date last changed
2021-03-31 02:41:42
@article{38d6f310-a41a-4261-92d3-09d3890fd217,
  abstract     = {<p>Disruption of intracellular calcium homeostasis is thought to play a role in neurodegenerative disorders such as Huntington's disease (HD). To study different aspects of putative pathogenic mechanisms in HD, we aimed to establish an in vitro model of calcium-induced toxicity in striatal neurons. The calcium ionophore A23187 induced a concentration- and time-dependent cell death in cultures of embryonic striatal neurons, causing both apoptosis and necrosis. Cell death was significantly reduced by the cell-permeant antioxidant manganese(III)tetrakis(4-benzoic acid) porphyrin (MnTBAP). Cyclosporin A and its analogue N-MeVal-4-cyclosporin also reduced the incidence of cell death, suggesting the participation of mitochondrial permeability transition in this process. Furthermore, addition of either of two types of caspase inhibitors, Ac-YVAD-CHO (acetyl-Tyr-Val-Ala-Asp-aldehyde) and Ac-DEVD-CHO (acetyl-Asp-Glu-Val-Asp-aldehyde), to the striatal cells blocked A23187-induced striatal cell death in a concentration-dependent manner. These results suggest that oxidative stress, opening of the mitochondrial permeability transition pore and activation of caspases are important steps in A23187-induced cell death. Copyright (C) 2000 Elsevier Science B.V.</p>},
  author       = {Petersén, Åsa and Castilho, Roger F. and Hansson, Oskar and Wieloch, Tadeusz and Brundin, Patrik},
  issn         = {0006-8993},
  language     = {eng},
  month        = {02},
  number       = {1-2},
  pages        = {20--29},
  publisher    = {Elsevier},
  series       = {Brain Research},
  title        = {Oxidative stress, mitochondrial permeability transition and activation of caspases in calcium ionophore A23187-induced death of cultured striatal neurons},
  url          = {http://dx.doi.org/10.1016/S0006-8993(99)02320-3},
  doi          = {10.1016/S0006-8993(99)02320-3},
  volume       = {857},
  year         = {2000},
}