The endoplasmic reticulum is the main site for caspase-3 activation following aluminum-induced neurotoxicity in rabbit hippocampus

Othman Ghribi, Mary M. Herman, John Savory

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

We have assessed the distribution of caspase-3 in subcellular fractions from rabbit brain hippocampus and find that in controls the pro-caspase-3 form is distributed mainly in the cytoplasm. In animals treated intracisternally with the neurotoxin aluminum-maltolate, although pro-caspase-3 levels are higher in the cytosolic fractions, p17, the active caspase-3, is localized mainly in the endoplasmic reticulum. This distribution is confirmed by immunohistochemistry which demonstrates the co-localization of p17 with calnexin, a specific marker of the endoplasmic reticulum. Based on the apparent translocation into the endoplasmic reticulum of active caspase-3, an executioner of cell death, the results suggest that this organelle is an important site in the caspase-3 mediated apoptosis cascade. Inhibition of the latter enzyme by directly targeting its main site of activation could represent a strategy to prevent this adverse event.

Original languageEnglish (US)
Pages (from-to)217-221
Number of pages5
JournalNeuroscience Letters
Volume324
Issue number3
DOIs
StatePublished - May 24 2002

Keywords

  • Aluminum
  • Apoptosis
  • Calnexin
  • Caspase-3
  • Cytosol
  • Endoplasmic reticulum
  • Hippocampus

ASJC Scopus subject areas

  • Neuroscience(all)

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