Differentially expressed genes in hippocampal cell cultures in response to an excitotoxic insult by quinolinic acid.
The NMDA-type glutamate receptor agonist quinolinic acid (QA), which causes tissue lesions in the rat brain as well as cell loss in neuronal cultures, is widely used in models of glutamate excitotoxicity. The aim of this study was to evaluate the alterations in gene expression in a primary hippocampal cell culture after exposure to QA. By means of differential mRNA display, we were able to pinpoint as many as 23 bands which appeared to be upregulated after a 6-h treatment with quinolinic acid. The differential expression of 13 cDNAs could be confirmed by dot blot and/or Northern analysis. Of the cDNAs, the p112 regulatory subunit of the 26S proteasome, a PDGF-associated protein and the glia-derived protease nexin PN-1 could be identified. The results provide emphasis to the participation of proteolysis and protease inhibition in neurodegenerative processes.
Institute of Medical Neurobiology, University of Magdeburg 'Otto von Guericke', Leipziger Strasse 44, D-39120, Magdeburg, Germany. bertolt.seidel@medizin.uni-magdeburg.de
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Seidel
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Keilhoff
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Reinheckel
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Wolf
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics; D002478:Cells, Cultured; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects*; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D010447:Peptide Hydrolases / Q000235:genetics; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D058255:Protease Nexins; D046988:Proteasome Endopeptidase Complex; D017378:Quinolinic Acid / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000187:drug effects*; D016335:Zinc Fingers
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D009498:Neurotoxins; D010982:Platelet-Derived Growth Factor; D058255:Protease Nexins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018698:Glutamic Acid; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D017378:Quinolinic Acid