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)

To clarify the functional significance of type IV phosphodiesterase (PDEIV) in neurons and glia cells [3H]rolipram binding and phosphodiesterase (PDE) activity were examined in cytosol and membrane fractions of neuroblastoma N18TG-2 and glioma C6Bu-1 cells. [3H]Rolipram binding was highly observed in cytosolic fractions of N18TG-2 compared to C6Bu-1. Binding was hardly observed in membrane fractions of both types of cells. Rolipram strongly (70%) inhibited the hydrolytic activity of cAMP in cytosolic fractions of N18TG-2. The activity in cytosol fractions of C6Bu-1 was slightly (20%) inhibited by rolipram. These results suggest that PDEIV plays important roles in neurons.
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PMID:[3H]Rolipram binding and phosphodiesterase activity in neuroblastoma N18TG-2 and glioma C6Bu-1. 752 96

Upregulation of the cAMP/protein kinase A (PKA) pathway has been shown to result in decreased proliferation, increased differentiation, and subsequent apoptosis of malignant glioma cells. Conventional cAMP analogs, however, are difficult to use in a clinical setting. Therefore, we investigated the effects of rolipram, a drug that has undergone clinical trials as an antidepressant and has also been proposed as a treatment for multiple sclerosis. Rolipram acts as a specific inhibitor of type IV phosphodiesterase (PDE4), leading to increased intracellular levels of cAMP. We report that the inhibition of PDE4 by rolipram results in the activation of the cAMP/PKA pathway, with potent stimulation of a reporter gene containing a cAMP-responsive element in its promoter region. Further, treatment of the human glioma cell line A-172 with rolipram results in increased expression of the cell cycle inhibitors p21(Cip1) and p27(KiP1), and decreased activity of cdk2, a cyclin-dependent kinase essential for cell cycle progression. As a result, the proliferation of A-172 cells is inhibited, with induction of a Gl block. Eventually, rolipram-treated A-172 cells undergo differentiation, which is followed by apoptotic cell death. As we observe this effect with other glioma cell cultures as well, our results suggest that rolipram could prove useful as a novel differentiating agent with both cytostatic and cytotoxic potential in the treatment of malignant gliomas.
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PMID:The type IV phosphodiesterase inhibitor rolipram induces expression of the cell cycle inhibitors p21(Cip1) and p27(Kip1), resulting in growth inhibition, increased differentiation, and subsequent apoptosis of malignant A-172 glioma cells. 1243 76

Previous studies have demonstrated that antidepressants can enhance glucocorticoid receptor (GR) translocation and function, possibly through activation of cAMP and downstream cAMP dependent protein kinases. Accordingly, we examined GR function in cells treated with rolipram, a phosphodiesterase (PDE) type 4 inhibitor that antagonizes cAMP breakdown. Compared with vehicle-treated cells, rolipram alone and in combination with dexamethasone significantly enhanced GR function as measured in both mouse L929 cells and rat C6 glioma cells stably transfected with reporter genes driven by upstream glucocorticoid response elements. Rolipram's facilitation of GR function was reversible by the GR antagonist, RU486, and was associated with reduced cytosloic GR binding, indicating rolipram enhancement of GR nuclear translocation. Finally, rolipram potently augmented GR enhancement by the antidepressant, desipramine. These findings broaden the potential pathways by which PDE type 4 inhibitors can influence cellular function and indicate that these agents may have special utility in disorders associated with impaired GR-mediated feedback inhibition.
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PMID:The phosphodiesterase type 4 inhibitor, rolipram, enhances glucocorticoid receptor function. 1246 51

Medulloblastoma is the most common brain tumor of childhood. Emerging molecular targets in medulloblastoma include neurotrophin and neuropeptide receptors. In the present study, we have examined the influence of brain-derived neurotrophic factor (BDNF)/TrkB receptor- and gastrin-releasing peptide receptor (GRPR)-mediated signaling on the viability of human medulloblastoma cells. The expression of TrkB and GRPR was confirmed by immunohistochemistry and mRNA for both BDNF and GRPR was detected by reverse transcriptase polymerase chain reaction in Daoy, D283, and ONS76 cells. Treatment with BDNF significantly inhibited the viability of Daoy and D283, but not ONS76 cells, measured with the MTT assay. Neither the GRPR agonists GRP and bombesin nor the GRPR antagonist RC-3095 affected cell viability. Because previous findings have indicated that the viability of glioma cells might be enhanced by GRP when combined with the cAMP phosphodiesterase-4 (PDE4) inhibitor rolipram, we also examined the effects of rolipram alone or combined with GRP on cell viability. Rolipram significantly reduced the viability of all three cell lines, and the inhibitory effect of rolipram in Daoy cells was not modified by cotreatment with GRP. The results suggest that BDNF/TrkB and PDE4, but not the GRPR, regulate the viability of medulloblastoma cells.
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PMID:BDNF and PDE4, but not the GRPR, regulate viability of human medulloblastoma cells. 1964 24