n-methyl-valyl-4-cyclosporin-a and Nerve-Degeneration

n-methyl-valyl-4-cyclosporin-a has been researched along with Nerve-Degeneration* in 1 studies

Other Studies

1 other study(ies) available for n-methyl-valyl-4-cyclosporin-a and Nerve-Degeneration

ArticleYear
Cyclosporin A and its nonimmunosuppressive analogue N-Me-Val-4-cyclosporin A mitigate glucose/oxygen deprivation-induced damage to rat cultured hippocampal neurons.
    The European journal of neuroscience, 1999, Volume: 11, Issue:9

    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.

    Topics: Animals; Cell Death; Cell Hypoxia; Cells, Cultured; Cyclophilins; Cyclosporine; Glucose; Hippocampus; Immunophilins; Immunosuppressive Agents; Mice; Mice, Inbred BALB C; Mitochondria; Mitochondrial Swelling; Nerve Degeneration; Neurons; Peptidyl-Prolyl Isomerase F; Rats

1999