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SUPEROXIDE-DISMUTASE DELAYS NEURONAL APOPTOSIS - A ROLE FOR REACTIVE OXYGEN SPECIES IN PROGRAMMED NEURONAL DEATH
Author(s): GREENLUND LJS, DECKWERTH TL, JOHNSON EM
Source: NEURON    Volume: 14    Issue: 2    Pages: 303-315    Published: FEB 1995  
Times Cited: 591     References: 56     
Abstract: Sympathetic neurons in culture die by apoptosis when deprived of nerve growth factor (NGF). We used this model of programmed cell death to study the mechanisms that mediate neuronal apoptosis. Cultured sympathetic neurons were injected with copper/zinc superoxide dismutase protein (SOD) or with an expression vector containing an SOD cDNA. In both cases apoptosis was delayed when the neurons were deprived of NGF. The delay was similar to that seen when a bcl-2 expression vector was injected. SOD, injected 8 hr after NGF deprivation, provided no protection, indicating that superoxide production may occur early in response to trophic factor deprivation. We have demonstrated, with a redox sensitive dye, an increase in reactive oxygen species (ROS) that peaked at 3 hr after sympathetic neurons were deprived of NGF. If NGF was added back to the culture medium after the period of peak ROS generation, apoptosis was completely prevented, suggesting that ROS production serves as an early signal, rather than a toxic agent, to mediate apoptosis.
Document Type: Article
Language: English
Reprint Address: GREENLUND, LJS (reprint author), WASHINGTON UNIV, SCH MED, DEPT NEUROL, ST LOUIS, MO 63110 USA
Addresses:
1. WASHINGTON UNIV, SCH MED, DEPT MOLEC BIOL & PHARMACOL, ST LOUIS, MO 63110 USA
Publisher: CELL PRESS, 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138
Subject Category: Neurosciences
IDS Number: QH294
ISSN: 0896-6273
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