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.
(Less)
- author
- Petersén, Åsa
LU
; Castilho, Roger F.
; Hansson, Oskar
LU
; Wieloch, Tadeusz
LU
and Brundin, Patrik
LU
- organization
- publishing date
- 2000-02-28
- 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
- 2024-10-03 05:05:22
@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}},
keywords = {{Apoptosis; Calcium; Cell death; Huntington's disease; Mitochondria; Striatal neuron}},
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}},
}