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Reactive oxygen species involved in the glutamate toxicity of C6 glioma cells via XC¯ antiporter system
- Source :
- Neuroscience. 73:201-208
- Publication Year :
- 1996
- Publisher :
- Elsevier BV, 1996.
-
Abstract
- We recently demonstrated that continuous t-glutamate exposure led to cell death in C6 glioma cells over a period of 24–36 h, due to inhibition of cystine uptake through the cystine/glutamate (xc¯) antiporter. The antioxidant vitamin E provided protection against this effect, supporting the hypothesis that depletion of glutathione might be responsible, resulting from insufficient cystine uptake. To clarify the content of oxidative stress after glutathione depletion, the present study was done to investigate accumulation and target molecules of reactive oxygen species induced by glutamate treatment. The accumulation of reactive oxygen species was increased three-fold as compared to a control culture. Membrane oxidation, as judged by lipid peroxidation, was increased two-fold after glutamate treatment. Cellular ATP content was significantly reduced by glutamate exposure. For the two cytosolic enzymes examined, activity of glyceraldehyde 3-phosphate dehydrogenase was slightly enhanced by glutamate treatment, while activity of glutamine synthetase was not changed. Impairment of nuclear DNA after glutamate exposure was also revealed by nuclear chromatin condensation with DNA fragmentation. Thus, the multiple targets (membrane, cytoplasm and nuclei) of oxygen radicals in glutamate toxicity through the xc¯antiporter system were evaluated for the first time. Furthermore, prevention from cell death and from cellular toxicity induced by oxygen radicals could be seen using three specific oxygen radical scavengers, catalase, 3,3,5,5-tetramethyl-pyrroline N-oxide and α-phenyl-N-t-butylnitrone, without restoring the glutathione deficit. This indicates that radical scavengers did not interact with the xc¯antiporter system, but directly scavenged the oxygen radicals. Taken together, the data strongly suggest that O2−, H202 and .OH accumulate in response to oxidative stress after glutathione depletion, resulting in glutamate cell death of C6 glioma cells.
- Subjects :
- Lipid Peroxides
Antioxidant
medicine.medical_treatment
Glutamic Acid
medicine.disease_cause
Antiporters
Lipid peroxidation
chemistry.chemical_compound
Adenosine Triphosphate
Glutamate-Ammonia Ligase
Glutamine synthetase
Tumor Cells, Cultured
medicine
Animals
Cell Nucleus
chemistry.chemical_classification
Reactive oxygen species
Cell Death
Brain Neoplasms
Chemistry
General Neuroscience
Glutamate receptor
Glyceraldehyde-3-Phosphate Dehydrogenases
Free Radical Scavengers
Glioma
Glutathione
Rats
Biochemistry
Cystine
NMDA receptor
Reactive Oxygen Species
Oxidative stress
DNA Damage
Subjects
Details
- ISSN :
- 03064522
- Volume :
- 73
- Database :
- OpenAIRE
- Journal :
- Neuroscience
- Accession number :
- edsair.doi.dedup.....48152a7e2c2827515b06875d60cef89b