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

30 Citations (Scopus)

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

Fingerprint

Aluminum
Caspase 3
Endoplasmic Reticulum
Hippocampus
Rabbits
Calnexin
Subcellular Fractions
Neurotoxins
Organelles
Cytoplasm
Cell Death
Immunohistochemistry
Apoptosis
Brain
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The endoplasmic reticulum is the main site for caspase-3 activation following aluminum-induced neurotoxicity in rabbit hippocampus. / Ghribi, Othman; Herman, Mary M.; Savory, John.

In: Neuroscience Letters, Vol. 324, No. 3, 24.05.2002, p. 217-221.

Research output: Contribution to journalArticle

@article{86b00b0b618c4c318afc6d5c5f639bcb,
title = "The endoplasmic reticulum is the main site for caspase-3 activation following aluminum-induced neurotoxicity in rabbit hippocampus",
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.",
keywords = "Aluminum, Apoptosis, Calnexin, Caspase-3, Cytosol, Endoplasmic reticulum, Hippocampus",
author = "Othman Ghribi and Herman, {Mary M.} and John Savory",
year = "2002",
month = "5",
day = "24",
doi = "10.1016/S0304-3940(02)00147-7",
language = "English (US)",
volume = "324",
pages = "217--221",
journal = "Neuroscience Letters",
issn = "0304-3940",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

TY - JOUR

T1 - The endoplasmic reticulum is the main site for caspase-3 activation following aluminum-induced neurotoxicity in rabbit hippocampus

AU - Ghribi, Othman

AU - Herman, Mary M.

AU - Savory, John

PY - 2002/5/24

Y1 - 2002/5/24

N2 - 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.

AB - 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.

KW - Aluminum

KW - Apoptosis

KW - Calnexin

KW - Caspase-3

KW - Cytosol

KW - Endoplasmic reticulum

KW - Hippocampus

UR - http://www.scopus.com/inward/record.url?scp=0037166054&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037166054&partnerID=8YFLogxK

U2 - 10.1016/S0304-3940(02)00147-7

DO - 10.1016/S0304-3940(02)00147-7

M3 - Article

C2 - 12009527

AN - SCOPUS:0037166054

VL - 324

SP - 217

EP - 221

JO - Neuroscience Letters

JF - Neuroscience Letters

SN - 0304-3940

IS - 3

ER -