Studies on acidic sulfur-containing amino acids, g-glutamyl- and b-aspartyl-containing peptides in brain
Abstract
The biological issue of this thesis is focused on the possible involvement of acidic sulfur-containing amino acids (ASCAAs), g-glutamyl (g-Glu)- and b-aspartyl (b-Asp)-containing peptides in excitatory amino acid neurotransmission and toxicity.g-Glu-cysteine, g-Glu-glutamine, g-Glu-glutamate, g-Glu-taurine, g-Glu-glycine, glutathione sulfonate, b-Asp-taurine, b-Asp-glycine and O-phosphoserine were identified in rat brain by improved reversed-phase high performance liquid chromatography using automated precolumn fluorescence labelling with o-phthaldialdehyde/b-mercaptoethanol. ASCAAs (cysteate, cysteine sulfinate, homocysteate, homocysteine sulfinate and O-sulfoserine), g-Glu-aspartate, g-Glu-cysteate, g-Glu-histidine and b-Asp-alanine were not identified at concentrations over 1 mM in rat brain. The functional implication of the presence of ASCAAs, g-Glu- and b-Asp-containing peptides in rat brain is discussed.Microdialysis experiments showed that the net efflux of g-Glu-cysteine, g-Glu-glutamine, g-Glu-glutamate, g-Glu-taurine (coeluting with g-Glu-glycine) and glutathione (GSH) increased from rat striatum during 30 minutes of cerebral ischemia. The net efflux of g-Glu-cysteine, g-Glu-glutamate and GSH from hippocampal slices was also elevated during high K+-induced depolarization and during anoxia/aglycemia in release experiments in vitro. A delayed increase in the net efflux of g-Glu-glutamate from hippocampal slices during high K+-induced depolarization was observed and the extracellular concentration of g-Glu-glutamate was over 3 orders of magnitude lower than that of glutamate. g-Glu-glutamate was found to activate N-methyl-D-aspartate (NMDA) receptors on neurons of rat olfactory bulb by using whole-cell patch clamp technique, showing that g-Glu-glutamate is an endogenous ligand of NMDA receptors. The possible transmitter or modulator functions and the possible excitotoxicity of g-Glu-containing dipeptides are discussed. Of the ASCAAs only the net efflux of cysteine sulfinate (CSA) from hippocampal slices during high K+-induced depolarization and during anoxia/aglycemia was observed. However, this efflux was partly inhibited by reducing agents added to the medium and in parallel with cysteine efflux, indicating spontaneous oxidation of cysteine to CSA rather than elevated release. The studies do not support ASCAAs as major transmitters in brain.Acivicin, a g-Glu transpeptidase blocker, reduced the net efflux of g-Glu-glutamate and g-Glu-glutamine, increased the net efflux of GSH from hippocampal slices during high K+-induced depolarization and during anoxia/aglycemia in vitro. Acivicin treatment also decreased the net efflux of cysteine and CSA during anoxia/aglycemia in vitro, but had no effect on the net efflux of glutamate during basal, high K+-induced depolarization, and during anoxia/aglycemia in vitro. The studies indicate that g-Glu transpeptidase regulates the extracellular concentrations of several g-Glu-containing peptides and cysteine in vitro, but do not support that this enzyme is involved in the uptake of amino acids such as glutamate in vitro.
University
Göteborgs universitet/University of Gothenburg
Institution
Department of Anatomy and Cell Biology
Institutionen för anatomi och cellbiologi
Date of defence
1997-06-04
Date
1997Author
Li, Xiaoying 1962-
Keywords
b-aspartyl-containing dipeptides
g-glutamyl-containing dipeptides
g-glutamyl transpeptidase
acivicin
anoxia/aglycemia
acidic sulfur-containing amino acids
cerebral ischemia
excitatory amino acids
excitotoxicity
glutathione
hippocampal slices
hi
Publication type
Doctoral thesis
Metadata
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