Trichostatin A stimulates steroid 5alpha-reductase gene expression in rat C6 glioma cells via a mechanism involving Sp1 and Sp3 transcription factors.
The adrenergic and serotonergic stimulations of rat C6 glioma cells have previously been shown to induce the activation of steroid 5alpha-reductase (5alpha-R) gene expression, resulting in their differentiation through the production of neuroactive 5alpha-reduced steroid metabolites. In addition, progesterone and histone deacetylase (HDAC) inhibitors have also been reported to promote the glial cell differentiation with the enhancement of serotonin-stimulated brain-derived neurotrophic factor gene transcription through the production of 5alpha-reduced neurosteroids, thus suggesting that glial cell differentiation is probably implicated in the protection and survival of neuronal cells in the brain. Therefore, the expression of 5alpha-R gene in glial cells seems physiologically important in maintaining the neural function in the brain, but little is known about the mechanism underlying the regulation of 5alpha-R gene transcription. In the present study, the effect of a HDAC inhibitor trichostatin A (TSA) on 5alpha-R gene transcription in the glioma cells was examined, and TSA was shown to induce the elevation of 5alpha-R mRNA levels through the activation of the 5alpha-R promoter via a mechanism involving Sp1 and Sp3 transcription factors in a time- and concentration-dependent manner. Thus, both Sp1 and Sp3 are considered to play a physiological role in the regulation of 5alpha-R gene expression, and hence the production of 5alpha-reduced neurosteroids in glial cells.
Her
Song
S
Division of Bio-Imaging, Chuncheon Center, Korea Basic Science Institute, Chuncheon, 200-701, South Korea.
Lee
Mi-Sook
MS
Morita
Kyoji
K
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D017353:Gene Deletion; D015870:Gene Expression / Q000187:drug effects*; D017930:Genes, Reporter; D005910:Glioma / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D051381:Rats; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D051705:Sp3 Transcription Factor / Q000235:genetics / Q000378:metabolism*
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D016329:Sp1 Transcription Factor; D051705:Sp3 Transcription Factor; C012589:trichostatin A; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; D006655:Histone Deacetylases