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Differences in the activation of the mitochondrial permeability transition among brain regions in the rat correlate with selective vulnerability

Friberg, Hans LU ; Connern, Cathal ; Halestrap, Andrew P. and Wieloch, Tadeusz LU (1999) In Journal of Neurochemistry 72(6). p.2488-2497
Abstract

Mitochondria from different regions of the brain were prepared, and the activation of the mitochondrial permeability transition (MPT) by calcium was investigated by monitoring the associated mitochondrial swelling. In general, the properties of the MPT in brain mitochondria were found to be qualitatively similar to those observed in liver and heart mitochondria. Thus, swelling was inhibited by adenine nucleotides (AdNs) and low pH (<7.0), whereas thiol reagents and alkalosis facilitated swelling. Cyclosporin A and its nonimmunosuppressive analogue N-methyl-Val-4-cyclosporin A (PKF 220- 384.) both inhibited swelling and prevented the translocation of cyclophilin D from the matrix to the membranes of cortical mitochondria. However, the... (More)

Mitochondria from different regions of the brain were prepared, and the activation of the mitochondrial permeability transition (MPT) by calcium was investigated by monitoring the associated mitochondrial swelling. In general, the properties of the MPT in brain mitochondria were found to be qualitatively similar to those observed in liver and heart mitochondria. Thus, swelling was inhibited by adenine nucleotides (AdNs) and low pH (<7.0), whereas thiol reagents and alkalosis facilitated swelling. Cyclosporin A and its nonimmunosuppressive analogue N-methyl-Val-4-cyclosporin A (PKF 220- 384.) both inhibited swelling and prevented the translocation of cyclophilin D from the matrix to the membranes of cortical mitochondria. However, the calcium sensitivity of the MPT differed in mitochondria from three brain regions (hippocampus > cortex > cerebellum) and is correlated with the susceptibility of these regions to ischemic damage. Depleting mitochondria of AdNs by treatment with pyrophosphate ions sensitized the MPT to [Ca2+] and abolished regional differences, implying regional differences in mitochondrial AdN content. This was confirmed by measurements showing significant differences in AdN content among regions (cerebellum > cortex > hippocampus). Our data add to recent evidence that the MPT may be involved in neuronal death.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Brain, Cyclophilin D, Cyclosporin A, Mitochondria, Mitochondrial permeability transition, Neuronal death
in
Journal of Neurochemistry
volume
72
issue
6
pages
10 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:0033007651
  • pmid:10349859
ISSN
0022-3042
DOI
10.1046/j.1471-4159.1999.0722488.x
language
English
LU publication?
yes
id
62569b34-315c-43af-ba7f-4c499dc529dc
date added to LUP
2019-06-13 16:54:38
date last changed
2024-04-02 09:34:53
@article{62569b34-315c-43af-ba7f-4c499dc529dc,
  abstract     = {{<p>Mitochondria from different regions of the brain were prepared, and the activation of the mitochondrial permeability transition (MPT) by calcium was investigated by monitoring the associated mitochondrial swelling. In general, the properties of the MPT in brain mitochondria were found to be qualitatively similar to those observed in liver and heart mitochondria. Thus, swelling was inhibited by adenine nucleotides (AdNs) and low pH (&lt;7.0), whereas thiol reagents and alkalosis facilitated swelling. Cyclosporin A and its nonimmunosuppressive analogue N-methyl-Val-4-cyclosporin A (PKF 220- 384.) both inhibited swelling and prevented the translocation of cyclophilin D from the matrix to the membranes of cortical mitochondria. However, the calcium sensitivity of the MPT differed in mitochondria from three brain regions (hippocampus &gt; cortex &gt; cerebellum) and is correlated with the susceptibility of these regions to ischemic damage. Depleting mitochondria of AdNs by treatment with pyrophosphate ions sensitized the MPT to [Ca<sup>2+</sup>] and abolished regional differences, implying regional differences in mitochondrial AdN content. This was confirmed by measurements showing significant differences in AdN content among regions (cerebellum &gt; cortex &gt; hippocampus). Our data add to recent evidence that the MPT may be involved in neuronal death.</p>}},
  author       = {{Friberg, Hans and Connern, Cathal and Halestrap, Andrew P. and Wieloch, Tadeusz}},
  issn         = {{0022-3042}},
  keywords     = {{Brain; Cyclophilin D; Cyclosporin A; Mitochondria; Mitochondrial permeability transition; Neuronal death}},
  language     = {{eng}},
  month        = {{06}},
  number       = {{6}},
  pages        = {{2488--2497}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Neurochemistry}},
  title        = {{Differences in the activation of the mitochondrial permeability transition among brain regions in the rat correlate with selective vulnerability}},
  url          = {{http://dx.doi.org/10.1046/j.1471-4159.1999.0722488.x}},
  doi          = {{10.1046/j.1471-4159.1999.0722488.x}},
  volume       = {{72}},
  year         = {{1999}},
}