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Cyclosporin A and its nonimmunosuppressive analogue N-Me-Val-4-cyclosporin A mitigate glucose/oxygen deprivation-induced damage to rat cultured hippocampal neurons

Khaspekov, Leonid ; Friberg, Hans LU ; Halestrap, Andrew ; Viktorov, Ilja and Wieloch, Tadeusz LU (1999) In European Journal of Neuroscience 11(9). p.3194-3198
Abstract

When mouse hippocampal neuronal cultures, 2-3 weeks in vitro, were transiently exposed to combined glucose and oxygen deprivation (100% argon, 5% CO2, in glucose-free medium) for 90 min, extensive neuronal degeneration had occurred after 24 h of reoxygenation. When these cultures were preincubated with cyclosporin A, a calcineurin inhibitor and a blocker of the mitochondrial permeability transition, neuronal death diminished by 30-50%. Similarly, the cyclosporin A analogue, N-Me-Val-4-cyclosporin A, a potent blocker of the mitochondrial permeability transition with no significant calcineurin blocking activity, decreased cell death by 70-80%. Both cyclosporin A and N-Me-Val-4-cyclosporin A markedly attenuated calcium-induced... (More)

When mouse hippocampal neuronal cultures, 2-3 weeks in vitro, were transiently exposed to combined glucose and oxygen deprivation (100% argon, 5% CO2, in glucose-free medium) for 90 min, extensive neuronal degeneration had occurred after 24 h of reoxygenation. When these cultures were preincubated with cyclosporin A, a calcineurin inhibitor and a blocker of the mitochondrial permeability transition, neuronal death diminished by 30-50%. Similarly, the cyclosporin A analogue, N-Me-Val-4-cyclosporin A, a potent blocker of the mitochondrial permeability transition with no significant calcineurin blocking activity, decreased cell death by 70-80%. Both cyclosporin A and N-Me-Val-4-cyclosporin A markedly attenuated calcium-induced swelling of isolated mouse brain mitochondria by blocking the mitochondrial permeability transition. The potassium thiocyanate-stabilized binding of cyclophilin D to mouse brain mitochondrial membranes was completely prevented by cyclosporin A and N-Me-Val-4-cyclosporin A. Our results strongly suggest that the mitochondrial permeability transition is involved in oxygen/glucose deprivation-induced cell death in vitro. Cyclophilin D and other components of the mitochondrial permeability transition may be important targets for neuroprotective and anti-ischaemic drugs.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Apoptosis, Cell cultures, Mitochondrial permeability transition, Neuronal death
in
European Journal of Neuroscience
volume
11
issue
9
pages
5 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:0032860116
  • pmid:10510183
ISSN
0953-816X
DOI
10.1046/j.1460-9568.1999.00743.x
language
English
LU publication?
yes
id
b5d14eed-ac99-42ee-a8e9-32a3ae1d3312
date added to LUP
2019-06-13 15:49:02
date last changed
2024-01-01 10:12:10
@article{b5d14eed-ac99-42ee-a8e9-32a3ae1d3312,
  abstract     = {{<p>When mouse hippocampal neuronal cultures, 2-3 weeks in vitro, were transiently exposed to combined glucose and oxygen deprivation (100% argon, 5% CO<sub>2</sub>, in glucose-free medium) for 90 min, extensive neuronal degeneration had occurred after 24 h of reoxygenation. When these cultures were preincubated with cyclosporin A, a calcineurin inhibitor and a blocker of the mitochondrial permeability transition, neuronal death diminished by 30-50%. Similarly, the cyclosporin A analogue, N-Me-Val-4-cyclosporin A, a potent blocker of the mitochondrial permeability transition with no significant calcineurin blocking activity, decreased cell death by 70-80%. Both cyclosporin A and N-Me-Val-4-cyclosporin A markedly attenuated calcium-induced swelling of isolated mouse brain mitochondria by blocking the mitochondrial permeability transition. The potassium thiocyanate-stabilized binding of cyclophilin D to mouse brain mitochondrial membranes was completely prevented by cyclosporin A and N-Me-Val-4-cyclosporin A. Our results strongly suggest that the mitochondrial permeability transition is involved in oxygen/glucose deprivation-induced cell death in vitro. Cyclophilin D and other components of the mitochondrial permeability transition may be important targets for neuroprotective and anti-ischaemic drugs.</p>}},
  author       = {{Khaspekov, Leonid and Friberg, Hans and Halestrap, Andrew and Viktorov, Ilja and Wieloch, Tadeusz}},
  issn         = {{0953-816X}},
  keywords     = {{Apoptosis; Cell cultures; Mitochondrial permeability transition; Neuronal death}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{9}},
  pages        = {{3194--3198}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{European Journal of Neuroscience}},
  title        = {{Cyclosporin A and its nonimmunosuppressive analogue N-Me-Val-4-cyclosporin A mitigate glucose/oxygen deprivation-induced damage to rat cultured hippocampal neurons}},
  url          = {{http://dx.doi.org/10.1046/j.1460-9568.1999.00743.x}},
  doi          = {{10.1046/j.1460-9568.1999.00743.x}},
  volume       = {{11}},
  year         = {{1999}},
}