Abstract
Gamma-aminobutyric acid type A (GABAA) receptor beta1 (gabrb1), a subunit of GABAA receptors involved in inhibitory effects on neurotransmission, was found to associate with the formation of protease-resistant prion protein in prion-infected neuroblastoma cells. Silencing of gabrb1 gene expression significantly decreased the abnormal prion protein level but paradoxically increased the normal prion protein level. Treatment with a gabrb1-specific inhibitor, salicylidene salicylhydrazide, dose-dependently decreased the abnormal prion protein level, but silencing of other GABAA receptor subunits' gene expression and treatments with the receptor antagonists and agonists did not. Therefore, gabrb1 involvement in abnormal prion protein formation is independent of GABAA receptors.
Copyright 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Brain Neoplasms / complications
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Brain Neoplasms / genetics
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Brain Neoplasms / metabolism*
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Cells, Cultured
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Drug Resistance / genetics
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GABA-A Receptor Antagonists
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Mice
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Mutant Proteins / genetics
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Mutant Proteins / metabolism
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Mutant Proteins / physiology
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Neuroblastoma / complications
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Neuroblastoma / genetics
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Neuroblastoma / metabolism*
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Peptide Hydrolases / metabolism
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Peptide Hydrolases / pharmacology
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Prion Diseases / complications
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Prion Diseases / genetics
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Prion Diseases / metabolism*
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Prion Proteins
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Prions / metabolism*
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Prions / physiology
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Protein Processing, Post-Translational / drug effects
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Protein Processing, Post-Translational / genetics
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RNA Interference / physiology
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RNA, Small Interfering / pharmacology
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Receptors, GABA-A / genetics
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Receptors, GABA-A / physiology*
Substances
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GABA-A Receptor Antagonists
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Gabrb1 protein, mouse
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Mutant Proteins
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Prion Proteins
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Prions
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Prnp protein, mouse
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RNA, Small Interfering
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Receptors, GABA-A
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Peptide Hydrolases