Co-involvement of mitochondria and endoplasmic reticulum in regulation of apoptosis

Changes in cytochrome c, Bcl-2 and Bax in the hippocampus of aluminum-treated rabbits

Ghribi Othman, David A. DeWitt, Michael S. Forbes, Mary M. Herman, John Savory

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Neurodegenerative diseases, including Alzheimer's disease, are characterized by a progressive and selective loss of neurons. Apoptosis under mitochondrial control has been implicated in this neuronal death process, involving the release of cytochrome c into the cytoplasm and initiation of the apoptosis cascade. However, a growing body of evidence suggests an active role for the endoplasmic reticulum in regulating apoptosis, either independent of mitochondrial, or in concert with mitochondrial-initiated pathways. Members of the Bcl-2 family of proteins have been shown to either inhibit apoptosis, as is the case with Bcl-2, or to promote it, in the case of Bax. Investigations in our laboratory have focused on neuronal injury resulting from the intracisternal administration of aluminum maltolate to New Zealand white rabbits, an animal system relevant to a study of human disease in that it reflects many of the histological and biochemical changes associated with Alzheimer's disease. Here we report that treatment of young adult rabbits with aluminum maltolate induces both cytochrome c translocation into brain cytosol, and caspase-3 activation. Furthermore, as assessed by Western blot analysis, these effects are accompanied by a decrease in Bcl-2 and an increase in Bax reactivity in the endoplasmic reticulum.

Original languageEnglish (US)
Pages (from-to)66-73
Number of pages8
JournalBrain Research
Volume903
Issue number1-2
DOIs
StatePublished - Jun 8 2001

Fingerprint

Cytochromes c
Aluminum
Endoplasmic Reticulum
Hippocampus
Mitochondria
Apoptosis
Rabbits
Alzheimer Disease
Caspase 3
Neurodegenerative Diseases
Cytosol
Young Adult
Cytoplasm
Western Blotting
Neurons
Wounds and Injuries
Brain
Proteins
aluminum maltolate
Therapeutics

Keywords

  • Aluminum
  • Alzheimer's disease
  • Bax
  • Bcl-2
  • Endoplasmic reticulum
  • Mitochondria

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Co-involvement of mitochondria and endoplasmic reticulum in regulation of apoptosis : Changes in cytochrome c, Bcl-2 and Bax in the hippocampus of aluminum-treated rabbits. / Othman, Ghribi; DeWitt, David A.; Forbes, Michael S.; Herman, Mary M.; Savory, John.

In: Brain Research, Vol. 903, No. 1-2, 08.06.2001, p. 66-73.

Research output: Contribution to journalArticle

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