Trichostatin A enhances glutamate transporter GLT-1 mRNA levels in C6 glioma cells via neurosteroid-mediated cell differentiation.
The neurotoxic effects of excitatory amino acids (EAAs) are suggested to be connected with the chronic loss of neuronal cells, thereby being responsible for the age-related neurodegenerative diseases. Therefore, it seems conceivable that the excitatory amino acid transporters may contribute to the protection of neuronal cells against the excitotoxic damage by facilitating the removal of EAAs from the brain tissue. On the other hand, previous studies have suggested that glial cell differentiation may be involved in the protection and recovery of neural function probably through the elevation of BDNF gene expression in the brain. Based on these findings, histone deacetylase (HDAC) inhibitors are assumed to induce glutamate transporter-1 (GLT-1) gene expression probably through the promotion of glial cell differentiation. Then, we examined the effects of HDAC inhibitors on GLT-1 mRNA levels in rat C6 glioma cells and found that trichostatin A can induce GLT-1 gene transcription following steroid 5α-reductase and GFAP gene expression. Therefore, it seems conceivable that glial cell differentiation may play a potential role in the removal of EAAs probably through the expression of GLT-1, thereby being involved in the protection of neuronal cells against the chronic excitotoxic insults in the brain.
Laboratory of Neuropharmacology, Department of Nursing, Shikoku University School of Health Sciences, Ohjin, Tokushima 771-1192, Japan.
Mari
M
Itoh
Takara
T
Hiroi
Naoyoshi
N
Nishibori
Takefumi
T
Sagara
Song
S
Her
Mi-Sook
MS
Lee
Kyoji
K
Morita
D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D042944:Cholestenone 5 alpha-Reductase / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D018846:Excitatory Amino Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005910:Glioma; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
D027342:Excitatory Amino Acid Transporter 2; D018846:Excitatory Amino Acids; D005904:Glial Fibrillary Acidic Protein; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; C493395:Slc1a2 protein, rat; C012589:trichostatin A; D042944:Cholestenone 5 alpha-Reductase