Cyclosporin A and its nonimmunosuppressive analogue N-Me-Val-4-cyclosporin A mitigate glucose/oxygen deprivation-induced damage to rat cultured hippocampal neurons
(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.
(Less)
- author
- Khaspekov, Leonid ; Friberg, Hans LU ; Halestrap, Andrew ; Viktorov, Ilja and Wieloch, Tadeusz LU
- organization
- publishing date
- 1999-09-01
- 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
- 2024-07-23 21:08:06
@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}}, }