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

Åsa Petersén, Roger F. Castilho, Oskar Hansson, Tadeusz Wieloch, Patrik Brundin

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)20-29
Number of pages10
JournalBrain Research
Volume857
Issue number1-2
DOIs
Publication statusPublished - 2000 Feb 28

Subject classification (UKÄ)

  • Neurosciences

Keywords

  • Apoptosis
  • Calcium
  • Cell death
  • Huntington's disease
  • Mitochondria
  • Striatal neuron

Fingerprint

Dive into the research topics of 'Oxidative stress, mitochondrial permeability transition and activation of caspases in calcium ionophore A23187-induced death of cultured striatal neurons'. Together they form a unique fingerprint.

Cite this