Cyclosporin A inhibits Al-induced cytochrome c release from mitochondria in aged rabbits

Othman Ghribi, David A. Dewitt, Michael S. Forbes, Ayala Arad, Mary M. Herman, John Savory

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Neurodegenerative diseases including Alzheimer's disease are characterized by a progressive and selective neuronal loss via an apoptosis mechanism, and there is a growing body of evidence which supports a central role of mitochondria in this apoptotic cell death. Release of cytochrome c from the mitochondria to the cytosol is considered a critical step in apoptosis. Here we report that aluminum maltolate induces cytochrome c translocation into the cytosol as early as 3 hours in aged but not in young rabbit hippocampus. Pretreatment with cyclosporin A, an inhibitor of the mitochondria permeability transition pore (MTP), blocks cytochrome c release. Therefore, it appears that aluminum maltolate-induced cytochrome c release results from opening of the MTP. This effect implicates aging as a prerequisite factor, since the MTP does not open in young animals. Mitochondrial injury thus may represent a primary initiator of neurodegeneration.

Original languageEnglish (US)
Pages (from-to)387-391
Number of pages5
JournalJournal of Alzheimer's Disease
Volume3
Issue number4
DOIs
StatePublished - Jan 1 2001

Fingerprint

Cytochromes c
Cyclosporine
Mitochondria
Rabbits
Permeability
Cytosol
Apoptosis
Neurodegenerative Diseases
Hippocampus
Alzheimer Disease
Cell Death
Wounds and Injuries
aluminum maltolate

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Cyclosporin A inhibits Al-induced cytochrome c release from mitochondria in aged rabbits. / Ghribi, Othman; Dewitt, David A.; Forbes, Michael S.; Arad, Ayala; Herman, Mary M.; Savory, John.

In: Journal of Alzheimer's Disease, Vol. 3, No. 4, 01.01.2001, p. 387-391.

Research output: Contribution to journalArticle

Ghribi, Othman ; Dewitt, David A. ; Forbes, Michael S. ; Arad, Ayala ; Herman, Mary M. ; Savory, John. / Cyclosporin A inhibits Al-induced cytochrome c release from mitochondria in aged rabbits. In: Journal of Alzheimer's Disease. 2001 ; Vol. 3, No. 4. pp. 387-391.
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