Abstract
Histone deacetylases (HDAC) inhibitors have been emerging as neuroprotective agents by acting on neurons and microglia. In this study, we found trichostatin A (TSA), a HDAC inhibitor, could inhibit the elevation of glutamate in 150 microM 1-methyl-4-phenylpyridinium (MPP+)-treated primary cultured astrocytes medium when its concentration reached 132 nM. TSA of 132 nM or more could promote the uptake of [3H]-D, L-glutamate by astrocytes. Further study showed the downregulation of glutamate transporter 1 and glutamate/aspartate transporter induced by MPP+ were prevented by TSA. Therefore, these findings suggested TSA could alleviate MPP+-induced impairment of astrocytic glutamate uptake, which might be a novel mechanism contributing to neuroprotection by HDAC inhibitors.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-Methyl-4-phenylpyridinium / pharmacology*
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Animals
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Astrocytes / cytology
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Astrocytes / drug effects*
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Astrocytes / metabolism
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Blotting, Western
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Cells, Cultured
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Chromatography, High Pressure Liquid
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Excitatory Amino Acid Transporter 1 / metabolism
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Excitatory Amino Acid Transporter 2 / metabolism
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Glutamic Acid / analysis
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Glutamic Acid / metabolism*
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Glutamic Acid / pharmacokinetics
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Histone Deacetylases / metabolism
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Hydroxamic Acids / pharmacology*
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Rats
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Rats, Wistar
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Up-Regulation / drug effects
Substances
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Enzyme Inhibitors
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Excitatory Amino Acid Transporter 1
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Excitatory Amino Acid Transporter 2
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Hydroxamic Acids
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Glutamic Acid
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trichostatin A
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Histone Deacetylases
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1-Methyl-4-phenylpyridinium