Effect of dibutyryl cyclic AMP and dexamethasone on glutamine synthetase gene expression in rat astrocytes in culture |
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Authors: | Marian J Jackson H Ronald Zielke Stephen R Max |
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Institution: | (1) Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland;(2) Department of Neurology, University of Maryland School of Medicine, 655 W. Baltimore St. Rm 12-019, 21201 Baltimore, Maryland;(3) Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland;(4) Hahnemann University, Philadelphia, Pennsylvania |
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Abstract: | Astrocytes are the primary site of glutamate conversion to glutamine in the brain. We examined the effects of treatment with either dibutyryl cyclic AMP and/or the synthetic glucocorticoid dexamethasone on glutamine synthetase enzyme activity and steady-state mRNA levels in cultured neonatal rat astrocytes. Treatment of cultures with dibutyryl cyclic AMP alone (0.25 mM–1.0 mM) increased glutamine synthetase activity and steady state mRNA levels in a dose-dependent manner. Similarly, treatment with dexamethasone alone (10–7–10–5 M) increased glutamine synthetase mRNA levels and enzyme activity. When astrocytes were treated with both effectors, additive increases in glutamine synthetase activity and mRNA were obtained. However, the additive effects were observed only when the effect of dibutyryl cyclic AMP alone was not maximal. These findings suggest that the actions of these effectors are mediated at the level of mRNA accumulation. The induction of glutamine synthetase mRNA by dibutyryl cyclic AMP was dependent on protein synthesis while the dexamethasone effect was not. Glucocorticoids and cyclic AMP are known to exert their effects on gene expression by different molecular mechanisms. Possible crosstalk between these effector pathways may occur in regulation of astrocyte glutamine synthetase expression.Abbreviations used GS
glutamine synthetase
- dbcAMP
dibutyryl cyclic AMP
- MEM
minimal essential medium
- cyx
cycloheximide
- GRE
glucocorticoid response element
- CRE
cyclic AMP response element |
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Keywords: | Glutamine synthetase astrocytes glucocorticoids cyclic AMP gene regulation |
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