Proteasome inhibition protects HT22 neuronal cells from oxidative glutamate toxicity

Oxidative stress caused by glutathione depletion after prolonged exposure to extracellular glutamate leads to a form of neuronal cell death that exhibits morphologically mixed features of both apoptosis and necrosis. However, specific downstream executioners involved in this form of cell death have...

Full description

Saved in:
Bibliographic Details
Published in:Journal of neurochemistry 2005-02, Vol.92 (4), p.824-830
Main Authors: Van Leyen, Klaus, Siddiq, Ambreena, Ratan, Rajiv R., Lo, Eng H.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
calpain
caspase
Cell Line
Cells, Cultured
Central nervous system
Central neurotransmission. Neuromudulation. Pathways and receptors
Cysteine Proteinase Inhibitors - pharmacology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
epoxomicin
Fundamental and applied biological sciences. Psychology
Glutamic Acid - toxicity
lactacystin
Medical sciences
MG132
Mice
Neurology
Neurons - drug effects
Neurons - enzymology
Oxidative Stress - drug effects
Oxidative Stress - physiology
oxytosis
Proteasome Endopeptidase Complex - metabolism
Proteasome Inhibitors
Rats
Vertebrates: nervous system and sense organs
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Oxidative stress caused by glutathione depletion after prolonged exposure to extracellular glutamate leads to a form of neuronal cell death that exhibits morphologically mixed features of both apoptosis and necrosis. However, specific downstream executioners involved in this form of cell death have yet to be identified. We report here that glutamate exposure does not activate caspase‐3 in the HT22 neuronal cell line. Furthermore, no cytoprotection was achieved with either the pan‐caspase inhibitor Z‐VAD‐fmk or the caspase‐3‐specific inhibitor DEVD‐CHO. In contrast, inhibition of the proteasome by lactacystin protected both HT22 cells and rat primary neuronal cells against cell lysis. In parallel, oxidatively altered and ubiquitinated proteins accumulated in the mitochondrial fraction of cells after proteasome inhibition. These findings suggest that caspases can be decoupled from oxidative stress under some conditions, and implicate the ubiquitin/proteasome pathway in neuronal cell death caused by oxidative glutamate toxicity.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2004.02915.x