Enhancement of glutamate uptake in 1-methyl-4-phenylpyridinium-treated astrocytes by trichostatin A.
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.
Wu
Jia-Yong
JY
Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing City, Jiangsu Province, 210008, PR China.
Niu
Feng-nan
FN
Huang
Rong
R
Xu
Yun
Y
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics; D006655:Histone Deacetylases / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects
D004791:Enzyme Inhibitors; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D006877:Hydroxamic Acids; D018698:Glutamic Acid; C012589:trichostatin A; D006655:Histone Deacetylases; D015655:1-Methyl-4-phenylpyridinium