Caspase-3-associated apoptotic cell death in excitotoxic necrosis of the entorhinal cortex following intraperitoneal injection of kainic acid in the rat

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Caspase-3-associated apoptotic cell death in excitotoxic necrosis of the entorhinal cortex following intraperitoneal injection of kainic acid in the rat. / Puig, B; Ferrer, I; Puig Martorell, Berta.

in: NEUROSCI LETT, Jahrgang 321, Nr. 3, 22.03.2002, S. 182-6.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

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@article{7b6dd1611f96437793c2cedecd6e5c65,
title = "Caspase-3-associated apoptotic cell death in excitotoxic necrosis of the entorhinal cortex following intraperitoneal injection of kainic acid in the rat",
abstract = "The present study is directed to study: (a) bax translocation and cytochrome c release as mediators of the mitochondrial pathway of apoptosis; (b) Fas-L (Fas-ligand) expression as an indicator of the possible involvement of the Fas/Fas-L signaling pathway; and (c) active caspase-3 expression as the main executioner of caspase-mediated apoptosis, in rats receiving an intraperitoneal injection of the glutamate analogue kainic acid (KA) at a dose of 9 mg/kg, which is sufficient to produce generalized seizures and excitotoxic cell death in the entorhinal cortex. Sub-fractionation studies of entorhinal cortex homogenates have shown cytochrome c and cytochrome oxidase IV localized in the mitochondrial fraction, and Bax localized in the cytosolic fraction. No modifications in the sub-cellular distribution of cytochrome c and Bax have been observed at 6 h and 24 h in KA-treated rats. Morphological studies have shown cytoplasmic shrinkage and nuclear condensation consistent with necrosis in the entorhinal cortex. Many neurons (about 30% of dying cells) are stained with the method of in situ end-labeling of nuclear DNA fragmentation. Yet only about 5% of dying cells have apoptotic morphology. A percentage of dying cells (5% at 6 h and 40% at 24 h) over-express Fas-L but only about 2% of dying cells at 24 h post-injection express cleaved caspase-3 (17 kD). The present data further support the concept that necrosis is the predominant form of cell death in the entorhinal cortex, although caspase-3-dependent apoptotic cell death may play a limited role, in the present paradigm of KA-induced excitotoxicity.",
keywords = "Animals, Apoptosis, Caspase 3, Caspases, Cytochrome c Group, Entorhinal Cortex, Fas Ligand Protein, Female, Glutamic Acid, Kainic Acid, Membrane Glycoproteins, Mitochondria, Necrosis, Neurons, Neurotoxins, Protein Transport, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Rats, Rats, Sprague-Dawley, Signal Transduction, bcl-2-Associated X Protein",
author = "B Puig and I Ferrer and {Puig Martorell}, Berta",
year = "2002",
month = mar,
day = "22",
language = "English",
volume = "321",
pages = "182--6",
journal = "NEUROSCI LETT",
issn = "0304-3940",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

RIS

TY - JOUR

T1 - Caspase-3-associated apoptotic cell death in excitotoxic necrosis of the entorhinal cortex following intraperitoneal injection of kainic acid in the rat

AU - Puig, B

AU - Ferrer, I

AU - Puig Martorell, Berta

PY - 2002/3/22

Y1 - 2002/3/22

N2 - The present study is directed to study: (a) bax translocation and cytochrome c release as mediators of the mitochondrial pathway of apoptosis; (b) Fas-L (Fas-ligand) expression as an indicator of the possible involvement of the Fas/Fas-L signaling pathway; and (c) active caspase-3 expression as the main executioner of caspase-mediated apoptosis, in rats receiving an intraperitoneal injection of the glutamate analogue kainic acid (KA) at a dose of 9 mg/kg, which is sufficient to produce generalized seizures and excitotoxic cell death in the entorhinal cortex. Sub-fractionation studies of entorhinal cortex homogenates have shown cytochrome c and cytochrome oxidase IV localized in the mitochondrial fraction, and Bax localized in the cytosolic fraction. No modifications in the sub-cellular distribution of cytochrome c and Bax have been observed at 6 h and 24 h in KA-treated rats. Morphological studies have shown cytoplasmic shrinkage and nuclear condensation consistent with necrosis in the entorhinal cortex. Many neurons (about 30% of dying cells) are stained with the method of in situ end-labeling of nuclear DNA fragmentation. Yet only about 5% of dying cells have apoptotic morphology. A percentage of dying cells (5% at 6 h and 40% at 24 h) over-express Fas-L but only about 2% of dying cells at 24 h post-injection express cleaved caspase-3 (17 kD). The present data further support the concept that necrosis is the predominant form of cell death in the entorhinal cortex, although caspase-3-dependent apoptotic cell death may play a limited role, in the present paradigm of KA-induced excitotoxicity.

AB - The present study is directed to study: (a) bax translocation and cytochrome c release as mediators of the mitochondrial pathway of apoptosis; (b) Fas-L (Fas-ligand) expression as an indicator of the possible involvement of the Fas/Fas-L signaling pathway; and (c) active caspase-3 expression as the main executioner of caspase-mediated apoptosis, in rats receiving an intraperitoneal injection of the glutamate analogue kainic acid (KA) at a dose of 9 mg/kg, which is sufficient to produce generalized seizures and excitotoxic cell death in the entorhinal cortex. Sub-fractionation studies of entorhinal cortex homogenates have shown cytochrome c and cytochrome oxidase IV localized in the mitochondrial fraction, and Bax localized in the cytosolic fraction. No modifications in the sub-cellular distribution of cytochrome c and Bax have been observed at 6 h and 24 h in KA-treated rats. Morphological studies have shown cytoplasmic shrinkage and nuclear condensation consistent with necrosis in the entorhinal cortex. Many neurons (about 30% of dying cells) are stained with the method of in situ end-labeling of nuclear DNA fragmentation. Yet only about 5% of dying cells have apoptotic morphology. A percentage of dying cells (5% at 6 h and 40% at 24 h) over-express Fas-L but only about 2% of dying cells at 24 h post-injection express cleaved caspase-3 (17 kD). The present data further support the concept that necrosis is the predominant form of cell death in the entorhinal cortex, although caspase-3-dependent apoptotic cell death may play a limited role, in the present paradigm of KA-induced excitotoxicity.

KW - Animals

KW - Apoptosis

KW - Caspase 3

KW - Caspases

KW - Cytochrome c Group

KW - Entorhinal Cortex

KW - Fas Ligand Protein

KW - Female

KW - Glutamic Acid

KW - Kainic Acid

KW - Membrane Glycoproteins

KW - Mitochondria

KW - Necrosis

KW - Neurons

KW - Neurotoxins

KW - Protein Transport

KW - Proto-Oncogene Proteins

KW - Proto-Oncogene Proteins c-bcl-2

KW - Rats

KW - Rats, Sprague-Dawley

KW - Signal Transduction

KW - bcl-2-Associated X Protein

M3 - SCORING: Journal article

C2 - 11880202

VL - 321

SP - 182

EP - 186

JO - NEUROSCI LETT

JF - NEUROSCI LETT

SN - 0304-3940

IS - 3

ER -