Glutamate induces the production of reactive oxygen species in cultured forebrain neurons following NMDA receptor activation
- PMID: 7751912
- PMCID: PMC6578215
- DOI: 10.1523/JNEUROSCI.15-05-03318.1995
Glutamate induces the production of reactive oxygen species in cultured forebrain neurons following NMDA receptor activation
Abstract
Using the fluorescent dye 2',7'-dichlorodihydrofluorescein (DCF-H2) we investigated the role of glutamate in the production of reactive oxygen species (ROS) in cultured neurons from fetal rat forebrain. The addition of an excitotoxic concentration of glutamate (100 microM) produced a generalized decrease in cellular DCF fluorescence accompanied by local areas of increased fluorescence around the margins of the cell body that could be observed within 2-4 min of glutamate exposure. Increases in fluorescence were dependent on NMDA receptor activation and Ca2+ entry and were blocked by the mitochondrial proton ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). Additional studies suggested that the generalized decrease in fluorescence was due to intracellular acidification. These studies suggest a critical role for mitochondria in the production of ROS in association with glutamate excitotoxicity, and additionally demonstrate the feasibility of measuring the production of ROS at the level of the single cell.
Similar articles
-
N-methyl-D-aspartate receptor-mediated mitochondrial Ca(2+) overload in acute excitotoxic motor neuron death: a mechanism distinct from chronic neurotoxicity after Ca(2+) influx.J Neurosci Res. 2001 Mar 1;63(5):377-87. doi: 10.1002/1097-4547(20010301)63:5<377::AID-JNR1032>3.0.CO;2-#. J Neurosci Res. 2001. PMID: 11223912
-
Excitotoxic death of a subset of embryonic rat motor neurons in vitro.J Neurochem. 1999 Feb;72(2):500-13. doi: 10.1046/j.1471-4159.1999.0720500.x. J Neurochem. 1999. PMID: 9930721
-
Ca2+ influx through glutamate receptor-associated channels in retina cells correlates with neuronal cell death.Eur J Pharmacol. 1996 Apr 29;302(1-3):153-62. doi: 10.1016/0014-2999(96)00044-1. Eur J Pharmacol. 1996. PMID: 8791003
-
Reverse Na+/Ca2+ exchange contributes to glutamate-induced intracellular Ca2+ concentration increases in cultured rat forebrain neurons.Mol Pharmacol. 1998 Apr;53(4):742-9. Mol Pharmacol. 1998. PMID: 9547366
-
Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases.Acta Pharmacol Sin. 2009 Apr;30(4):379-87. doi: 10.1038/aps.2009.24. Acta Pharmacol Sin. 2009. PMID: 19343058 Free PMC article. Review.
Cited by
-
Neuron Activity Dependent Redox Compartmentation Revealed with a Second Generation Red-Shifted Ratiometric Sensor.ACS Chem Neurosci. 2020 Sep 2;11(17):2666-2678. doi: 10.1021/acschemneuro.0c00342. Epub 2020 Aug 21. ACS Chem Neurosci. 2020. PMID: 32786310 Free PMC article.
-
Incorporation of cofilin into rods depends on disulfide intermolecular bonds: implications for actin regulation and neurodegenerative disease.J Neurosci. 2012 May 9;32(19):6670-81. doi: 10.1523/JNEUROSCI.6020-11.2012. J Neurosci. 2012. PMID: 22573689 Free PMC article.
-
The specificity of neuroprotection by antioxidants.J Biomed Sci. 2009 Nov 5;16(1):98. doi: 10.1186/1423-0127-16-98. J Biomed Sci. 2009. PMID: 19891782 Free PMC article.
-
Methamphetamine causes depletion of glutathione and an increase in oxidized glutathione in the rat striatum and prefrontal cortex.Neurotox Res. 2001 Jul;3(3):277-80. doi: 10.1007/BF03033266. Neurotox Res. 2001. PMID: 15111252
-
Excitotoxic insults lead to peroxiredoxin hyperoxidation.Oxid Med Cell Longev. 2009 Apr-Jun;2(2):110-3. doi: 10.4161/oxim.2.2.8300. Oxid Med Cell Longev. 2009. PMID: 20357934 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Miscellaneous
