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Cyclosporin A, but not FK 506, protects mitochondria and neurons against hypoglycemic damage and implicates the mitochondrial permeability transition in cell death

Friberg, Hans LU ; Ferrand-Drake, Michel LU ; Bengtsson, Finn LU ; Halestrap, Andrew P. and Wieloch, Tadeusz LU (1998) In The Journal of Neuroscience 18(14). p.5151-5159
Abstract

Induction of the mitochondrial permeability transition (MPT) has been implicated in cellular apoptosis and in ischemia-reperfusion injury. During MPT, a channel in the inner mitochondrial membrane, the mitochondrial megachannel, opens and causes isolated mitochondria to swell. MPT and mitochondrial swelling is inhibited by cyclosporin A (CsA), which may also inhibit apoptosis in some cells. Treatment with CsA (50 mg/kg, i.v.) showed a robust reduction of brain damage when administered 30 min before insulin- induced hypoglycemic isoelectricity of 30 min duration. Ultrastructural examination of the dentate gyrus revealed a marked swelling of dendrites and mitochondria during the hypoglycemic insult. In CsA-treated animals, mitochondria... (More)

Induction of the mitochondrial permeability transition (MPT) has been implicated in cellular apoptosis and in ischemia-reperfusion injury. During MPT, a channel in the inner mitochondrial membrane, the mitochondrial megachannel, opens and causes isolated mitochondria to swell. MPT and mitochondrial swelling is inhibited by cyclosporin A (CsA), which may also inhibit apoptosis in some cells. Treatment with CsA (50 mg/kg, i.v.) showed a robust reduction of brain damage when administered 30 min before insulin- induced hypoglycemic isoelectricity of 30 min duration. Ultrastructural examination of the dentate gyrus revealed a marked swelling of dendrites and mitochondria during the hypoglycemic insult. In CsA-treated animals, mitochondria resumed a normal and contracted appearance during and after the hypoglycemic insult. Treatment with FK 506 (2 mg/kg, i.v.), a compound with immunosuppressive action similar to that of CsA, was not protective. Studies on the swelling kinetics of isolated mitochondria from the hippocampus showed that CsA, but not FK 506, inhibits calcium ion-induced MPT. We conclude that CsA treatment during hypoglycemic coma inhibits the MPT and reduces damage and that mitochondria and the MPT are likely to be involved in the development of hypoglycemic brain damage in the rat.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
keywords
Brain damage, Cell death, Cyclosporin A, Hippocampal mitochondria, Hypoglycemia, Mitochondrial permeability transition
in
The Journal of Neuroscience
volume
18
issue
14
pages
9 pages
publisher
Society for Neuroscience
external identifiers
  • pmid:9651198
  • scopus:0032528154
ISSN
0270-6474
language
English
LU publication?
yes
id
73fa89ae-4d69-4f6a-b346-9d24c1b57774
date added to LUP
2016-10-05 16:04:58
date last changed
2025-04-05 20:19:34
@article{73fa89ae-4d69-4f6a-b346-9d24c1b57774,
  abstract     = {{<p>Induction of the mitochondrial permeability transition (MPT) has been implicated in cellular apoptosis and in ischemia-reperfusion injury. During MPT, a channel in the inner mitochondrial membrane, the mitochondrial megachannel, opens and causes isolated mitochondria to swell. MPT and mitochondrial swelling is inhibited by cyclosporin A (CsA), which may also inhibit apoptosis in some cells. Treatment with CsA (50 mg/kg, i.v.) showed a robust reduction of brain damage when administered 30 min before insulin- induced hypoglycemic isoelectricity of 30 min duration. Ultrastructural examination of the dentate gyrus revealed a marked swelling of dendrites and mitochondria during the hypoglycemic insult. In CsA-treated animals, mitochondria resumed a normal and contracted appearance during and after the hypoglycemic insult. Treatment with FK 506 (2 mg/kg, i.v.), a compound with immunosuppressive action similar to that of CsA, was not protective. Studies on the swelling kinetics of isolated mitochondria from the hippocampus showed that CsA, but not FK 506, inhibits calcium ion-induced MPT. We conclude that CsA treatment during hypoglycemic coma inhibits the MPT and reduces damage and that mitochondria and the MPT are likely to be involved in the development of hypoglycemic brain damage in the rat.</p>}},
  author       = {{Friberg, Hans and Ferrand-Drake, Michel and Bengtsson, Finn and Halestrap, Andrew P. and Wieloch, Tadeusz}},
  issn         = {{0270-6474}},
  keywords     = {{Brain damage; Cell death; Cyclosporin A; Hippocampal mitochondria; Hypoglycemia; Mitochondrial permeability transition}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{14}},
  pages        = {{5151--5159}},
  publisher    = {{Society for Neuroscience}},
  series       = {{The Journal of Neuroscience}},
  title        = {{Cyclosporin A, but not FK 506, protects mitochondria and neurons against hypoglycemic damage and implicates the mitochondrial permeability transition in cell death}},
  volume       = {{18}},
  year         = {{1998}},
}