Trichostatin A Enhances Glutamate Transporter GLT-1 mRNA Levels in C6 Glioma Cells via Neurosteroid-Mediated Cell Differentiation
- 341 Downloads
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.
KeywordsTrichostatin A Glial cell differentiation GLT-1 gene expression Neuroprotective function Excitotoxic damage
This work was supported in part by the funds provided by Kohken Co. Inc. (Sapporo, Japan) and Navio Co. Ltd. (Hiroshima, Japan).
Conflict of Interest Statement
There is no conflict of interest associated with the authors of this paper, and the fund sponsors did not cause any inappropriate influence on this work.
- Kaur P, Jodhka PK, Underwood WA, Bowles CA, de Fiebre NC, de Fiebre CM, Singh M (2007) Progesterone increases brain-derived neurotrophic factor expression and protects against glutamate toxicity in a mitogen-activated protein kinase- and phosphoinositide-3 kinase-dependent manner in cerebral cortical explants. J Neurosci Res 85:2441–2449PubMedCrossRefGoogle Scholar
- Kim K, Lee SG, Kegelman TP, Su ZZ, Das SK, Dash R, Dasgupta S, Barral PM, Hedvat M, Diaz P, Reed JC, Stebbins JL, Pellecchia M, Sarkar D, Fisher PB (2011) Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics. J Cell Physiol 226:248–293CrossRefGoogle Scholar