Glutamate uptake inhibition by oxygen free radicals in rat cortical astrocytes
Details
Serval ID
serval:BIB_7F27D82693AA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Glutamate uptake inhibition by oxygen free radicals in rat cortical astrocytes
Journal
Journal of Neuroscience
ISSN
0270-6474 (Print)
Publication state
Published
Issued date
05/1994
Volume
14
Number
5 Pt 1
Pages
2924-32
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Research Support, Non-U.S. Gov't --- Old month value: May
Abstract
Formation of reactive oxygen species and disfunction of the excitatory amino acid (EAA) system are thought to be key events in the development of neuronal injury in several acute and long-term neurodegenerative diseases. Recent evidence suggests that the two phenomena may be interdependent. The present study is aimed at exploring possible molecular mechanisms underlying oxygen radical-EAA interaction. Exposure of cortical astrocytic cultures to either xanthine + xanthine oxidase (X/XO), a free radical-generating system, or hydrogen peroxide (H2O2) results in a marked decrease of high-affinity glutamate transport. Within 10 min of X/XO application, uptake falls to approximately 60% of its control value. In parallel no detectable release of lactate dehydrogenase occurs. X/XO effect is abolished in the presence of a mixture of scavenger enzymes (superoxide dismutase+catalase) or by the disulfide-reducing agents glutathione and dithiothreitol (DTT), but not by lipophilic antioxidants or ascorbate. The time course of inhibition shows an almost linear decline of glutamate transport during cell exposure to free radicals, while upon their inactivation the decline stops but established inhibition persists for at least 1 hr. In this situation, application of DTT significantly restores transport function. These data suggest that free radicals inhibit glutamate uptake primarily by long-lasting oxidation of protein sulfhydryl (SH) groups. Chemical modifiers of free SH groups, such as p-chloromercuribenzoate and N-ethylmaleimide, also induce uptake inhibition. Na+/K+ ATPase is a known target of oxygen radicals and may be involved in glutamate uptake inhibition. Indeed, ouabain, a blocker of the pump, reduces uptake in astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Keywords
2-Amino-5-phosphonovalerate/pharmacology
6-Cyano-7-nitroquinoxaline-2,3-dione
Animals
Animals, Newborn
Antioxidants/*pharmacology
Astrocytes/drug effects/*metabolism
Biological Transport/drug effects
Catalase/pharmacology
Cells, Cultured
Cerebral Cortex/*metabolism
Chloromercuribenzoates/pharmacology
Dithionitrobenzoic Acid/pharmacology
Dithiothreitol/pharmacology
Ethylmaleimide/pharmacology
Free Radical Scavengers
Free Radicals/pharmacology
Glutamates/*metabolism
Glutamic Acid
Glutathione/pharmacology
Hydrogen Peroxide/*pharmacology
Kinetics
L-Lactate Dehydrogenase/analysis
Quinoxalines/pharmacology
Rats
Superoxide Dismutase/pharmacology
Time Factors
Xanthine
Xanthine Oxidase/pharmacology
Xanthines/pharmacology
p-Chloromercuribenzoic Acid
Pubmed
Web of science
Create date
24/01/2008 15:37
Last modification date
20/08/2019 15:40