Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat C6 glioma cells are considered to be well characterized, and therefore commonly used as a model system to investigate the function of glial cells. However, recent study has shown that an alteration in the expression of their phenotypic antigens is observed when the cells are maintained under the serum-free conditions, proposing the possibility that various properties of glioma cells can be altered by the growth conditions. To test this possibility, the effects of serum-free culture conditions on the expression of steroid 5alpha-reductase (5alpha-R) type 1 isozyme in glioma cells were examined using immunocytochemical technique. Immunoreactivity of 5alpha-R type 1 was confined to the perinuclear region of glioma cells cultured in serum-containing medium, and observed in the cytoplasmic space as well as the perinuclear region of the cells cultured in serum-free medium. In contrast, serum deprivation failed to affect the expression of phenotypic antigens, glial fibrillary acidic protein (GFAP) and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase). Further studies showed that the expression of cytoplasmic 5alpha-R immunoreactivity induced by serum deprivation was reversible, and might be attributed to removal of serum proteins rather than biologically active small molecules from culture medium. This alteration in the expression of 5alpha-R immunoreactivity is therefore considered to reflect the translocation of the enzyme from the perinuclear region to the cell cytoplasm rather than the induction of cytoplasmic enzyme, and suggest that the culture conditions cause an alteration in the subcellular localization of 5alpha-R type 1 isozyme without phenotypic change of the glioma cell.
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PMID:Influence of serum-free culture conditions on subcellular localization of steroid 5alpha-reductase in rat C6 glioma cells. 972 33

Immunocytochemical studies previously showed that serum deprivation resulted in the appearance of steroid 5alpha-reductase (5alpha-R) in the cytoplasm of rat C6 glioma cells. To determine whether this increase in cytoplasmic 5alpha-R was due to changes in 5alpha-R gene expression, the effect of serum deprivation on 5alpha-R mRNA expression was examined. No significant change in the mRNA levels was observed in cells grown in serum-free culture medium. Therefore, the appearance of 5alpha-R immunoreactivity in the cell cytoplasm observed under serum-free conditions is probably not due to changes in 5alpha-R gene expression.
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PMID:Influence of serum-free culture conditions on steroid 5alpha-reductase mRNA expression in rat C6 glioma cells. 1035 May 72

Steroid 5alpha-reductase (5alpha-R) is well known as the enzyme converting progesterone and other steroid hormones to their 5alpha-reduced metabolites and has been reported to be localized in both neuronal and glial cells in the brain. Previously, the enzyme activity in glial cells has been shown to be enhanced either by coculturing with neuronal cells or by adding the conditioned medium of neuronal cells, suggesting a possible implication of neuro-glial interactions in the regulation of neurosteroid metabolism in the brain. In the present studies, the effects of adrenergic agonists on 5alpha-R mRNA and protein levels in rat C6 glioma cells were examined as one of the model experiments for investigating the influence of neuronal activity on the expression of 5alpha-R gene in the glial cell. The direct challenge of beta-adrenergic agonists to glioma cells resulted in the rapid and transient elevation of 5alpha-R mRNA levels through the activation of the cyclic AMP (cAMP)/protein kinase A-mediated signaling pathway. Further studies showed that cAMP-induced 5alpha-R mRNA expression was completely abolished by pretreatment of cells with actinomycin D and also indicated that the elevation of 5alpha-R mRNA levels was accompanied by an increase in enzyme protein in the cells. These findings provide strong evidence that the stimulation of beta-adrenergic receptors might induce the transcriptional activation of 5alpha-R gene expression in glial cells, proposing the possibility that neuronal activity might be involved in the production of neuroactive 5alpha-reduced steroids in the brain.
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PMID:Adrenergic activation of steroid 5alpha-reductase gene expression in rat C6 glioma cells: involvement of cyclic amp/protein kinase A-mediated signaling pathway. 1499 14

Steroid 5alpha-reductase type 1 (5alpha-R), the enzyme converting progesterone and other steroid hormones to their 5alpha-reduced metabolites, has been shown to be localized in both neuronal and glial cells, and this enzyme in glial cells has previously been reported to be activated either by co-culturing with neuronal cells or by adding the conditioned medium of neuronal cells, thus suggesting that neuronal activity may be implicated in the regulation of neurosteroid metabolism in brain. In the present study, to investigate a potential role of neurotrophic factors in the mechanism regulating the production of neuroactive 5alpha-reduced steroid metabolites, the direct action of NGF on 5alpha-R gene expression was examined by measuring the steady-state levels of 5alpha-R mRNA levels in rat C6 glioma cells. Exposure of the glioma cells to NGF increased both 5alpha-R mRNA and its protein levels, and induced the transient elevation of Egr-1 mRNA levels prior to the expression of 5alpha-R mRNA in the cells. Furthermore, NGF failed to induce any significant elevation of 5alpha-R mRNA levels in the cells pretreated with Egr-1 antisense oligodeoxynucleotides. These findings indicate that NGF induces the elevation of 5alpha-R gene expression in the glioma cells through the expression of transcription factor Egr-1, proposing the possibility that NGF, and probably other neurotrophic factors as well, may play a potential role in the regulation of 5alpha-reduced steroid production as one of the factors mediating the intercellular communication between neuronal and glial cells in the brain.
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PMID:Nerve growth factor induces elevation of steroid 5alpha-reductase mRNA levels in rat C6 glioma cells through expression of transcription factor Egr-1. 1524 39

Brain neurosteroids modulate gamma-aminobutyric acid type A (GABAA) receptor activity, thereby playing a role in mood disorders. Alterations in 17beta-estradiol (E2) and progesterone (P) are also known to play a significant role in psychopathology in women. The aim of the present study was to evaluate the synthesis of dihydroprogesterone (DHP), tetrahydroprogesterone (THP), and the activity of 5alpha-reductase (5alphaR) which regulates the reduction of P to DHP on exposure to supraphysiological levels of E2 in vitro (C6 glioma cells) and in vivo (mouse brain). The results showed that supraphysiological levels of E2 induced a decrease in the accumulation of both neurosteroids, probably by decreasing the activity of 5alphaR. We hypothesize that the high levels of E2 in pregnancy attenuate the increase in the conversion of P to THP in the brain and that the ratio of E2/P modulates the sedative effect of THP. This process may be relevant to psychopathological disorders that are ascribed to drastic alterations in estrogen levels, such as premenstrual syndrome, pregnancy-related mental disorders, and postpartum "blues".
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PMID:Influence of 17beta-estradiol on the synthesis of reduced neurosteroids in the brain (in vivo) and in glioma cells (in vitro): possible relevance to mental disorders in women. 1531 99

Selective serotonin reuptake inhibitors (SSRIs) are widely used for the treatment of depressive mood disorders and well known to inhibit the reuptake of neurotransmitter serotonin into nerve terminals. Thus, it seems conceivable that these drugs may induce the outflow of serotonin from the synapse as a consequence of inhibiting the reuptake, resulting in the stimulation of glial cells surrounding nerve terminals. On this hypothesis, the effect of serotonin on steroid 5alpha-reductase type 1 (5alpha-R) gene expression in rat C6 glioma cells was examined as one of the in vitro model experiments for investigating the indirect influence of SSRIs on glial cells. Serotonin elevated 5alpha-R mRNA and protein levels through the stimulation of serotonin 5-HT2A receptors, and also elevated Egr-1 mRNA and protein levels prior to 5alpha-R gene expression in the glioma cells. Furthermore, serotonin failed to significantly increase 5alpha-R mRNA levels in the cells preloaded with the antisense oligodeoxynucleotide targeted on Egr-1 gene. These results indicate that serotonin may stimulate 5alpha-R gene expression via transcription factor Egr-1 in glial cells, thus suggesting that serotonin flowing out of the serotonergic synapse may be implicated in SSRI-induced changes in neurosteroid metabolism in brain.
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PMID:Serotonergic 5-HT2A receptor stimulation induces steroid 5alpha-reductase gene expression in rat C6 glioma cells via transcription factor Egr-1. 1593 12

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.
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PMID:Trichostatin A stimulates steroid 5alpha-reductase gene expression in rat C6 glioma cells via a mechanism involving Sp1 and Sp3 transcription factors. 1972 74