Jackson M J, Zielke H R, Max S R
Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, USA.
Neurochem Res. 1995 Feb;20(2):201-7. doi: 10.1007/BF00970545.
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.
星形胶质细胞是大脑中谷氨酸转化为谷氨酰胺的主要场所。我们研究了用二丁酰环磷腺苷和/或合成糖皮质激素地塞米松处理对培养的新生大鼠星形胶质细胞中谷氨酰胺合成酶活性和稳态mRNA水平的影响。单独用二丁酰环磷腺苷（0.25 mM - 1.0 mM）处理培养物，以剂量依赖的方式增加了谷氨酰胺合成酶活性和稳态mRNA水平。同样，单独用地塞米松（10(-7)-10(-5) M）处理增加了谷氨酰胺合成酶mRNA水平和酶活性。当星形胶质细胞用两种效应物处理时，谷氨酰胺合成酶活性和mRNA出现相加性增加。然而，仅当单独使用二丁酰环磷腺苷的效应未达到最大时才观察到相加效应。这些发现表明这些效应物的作用是在mRNA积累水平介导的。二丁酰环磷腺苷对谷氨酰胺合成酶mRNA的诱导依赖于蛋白质合成，而地塞米松的效应则不依赖。已知糖皮质激素和环磷腺苷通过不同的分子机制对基因表达发挥作用。这些效应物途径之间可能存在相互作用，参与星形胶质细胞谷氨酰胺合成酶表达的调节。
