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| Abstract |
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| Title: | Reduced cholesterol content and the effects of inhibitors on Na+ dependent glutamate transport in rat brain nerve terminals |
| Author: | Roman Sivko ; Natalia Krisanova ; Tatiana Borisova |
| Abstract: | The influence of the inhibitors DL-threo-b-benzyloxyaspartate (DL-TBOA) and DL-threo-b-hydroxyaspartate (DL-THA) on Na+-dependent glutamate transport was investigated in synaptosomes losing one quarter of membrane cholesterol after half an hour treatment by 15 mM methyl-b-cyclodextrin (MbCD, MbetaCD). Despite significant decrease in the initial velocity of glutamate uptake (49 ± 4% at 100 uM L-[14C]glutamate), cholesterol-depleted synaptosomes retained the ability to accumulate and keep the neurotransmitter inside during loading with L-[14C]glutamate reaching concentration of 1.2 ± 0,1 nmol/mg of protein in control and 1.1±0,1 nmol/mg of protein in treated synaptosomes. After cholesterol extraction, stimulated by depolarization transporter-mediated release of preloaded L-[14C]glutamate from synaptosomes became more sensitive to DL-TBOA (100 uM), which inhibited release by 40 ± 4 % of total in control and 55 ± 4 % after application of MbCD. L-[14C]glutamate uptake by treated synaptosomes demonstrated similar sensitivity with controls to DL-TBOA and DL-THA. We suggested that an increase in the inhibitory effects of DL-TBOA on transporter-mediated glutamate release uncovered a decrease in the activity of reverse transporters in cholesterol-depleted synaptosomes, which might remain unnoticeable in the absence of the inhibitor.Key words: cholesterol, methyl-beta-cyclodextrin, L-glutamate, Na+-dependent transporters, uptake, transporter-mediated release, rat brain synaptosomes |
| Journal: | Neurobiology of Lipids |
| Issn: | 16835506 |
| EIssn: | |
| Year: | 2009 |
| Volume: | 8 |
| Issue: | |
| pages/rec.No: | 2 |
| Key words | cholesterol ; methyl-beta-cyclodextrin ; L-glutamate ; Na+ dependent transporters ; uptake ; transporter-mediated release ; rat brain synaptosomes |
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