Excitatory amino acid receptor activation produces a selective and long-lasting modulation of gene expression in hippocampal neurons
| Autor: | Emma R. Jakoi, Sompong Sombati, Claudia M. Gerwin, Robert J. DeLorenzo |
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| Rok vydání: | 1992 |
| Předmět: |
Time Factors
Cell Survival Biotin Down-Regulation Glutamic Acid Stimulation Hippocampal formation Biology Hippocampus Glutamates Gene expression medicine Animals Receptors Amino Acid RNA Messenger Receptor Molecular Biology Neurons General Neuroscience Glutamate receptor Membrane Proteins DNA Rats Cell biology medicine.anatomical_structure Gene Expression Regulation Biochemistry Excitatory postsynaptic potential RNA NMDA receptor Neurology (clinical) Neuron DNA Probes Developmental Biology |
| Zdroj: | Brain Research. 582:282-290 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/0006-8993(92)90145-y |
| Popis: | Activation of excitatory amino acid (EAA) receptors in cultured hippocampal neurons causes down-regulation of the protein ligatin, a receptor for phosphoglycoproteins and a marker protein for membrane-vesicle transport systems. This reduction occurs at both physiologic and excitotoxic levels of glutamate stimulation and is accompanied by a significant decrease in steady state levels of ligatin mRNA. Reduction in ligatin mRNA occurs within 60 min and persists 24 h later. Steady state levels of mRNAs encoding cyclophilin, an ubiquitous cytosolic protein, and neuron specific-enolase (N-SE) are not diminished by glutamate receptor activation, demonstrating that down-regulation of ligatin mRNA was not a result of general catabolism. Further, this reduction in ligatin mRNA occurred without induction of HSP 70. Pharmacological studies using selective antagonists and agonists indicate that this down-regulation of ligatin gene expression is predominantly mediated by theN-methyl- d -aspartate (NMDA) subclass of EAA receptors and that Ca2+ is required. This is the first report that EAA receptor activation in hippocampal neurons can pretranslationally down-regulate gene expression in a rapid and long-lasting manner under physiologic, as well as cytotoxic conditions. The data support the hypothesis that modulation of neuronal gene expression may represent a molecular mechanism mediating some of the long-lasting functional and pathophysiological effects of EAA on cell function. |
| Databáze: | OpenAIRE |
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