The First Clinical Medical College of Fujian Medical University, Fuzhou, China.
The First Clinical Medical College of Fujian Medical University, Fuzhou, China; Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.
Biochem Biophys Res Commun. 2014 Jul 18;450(1):295-9. doi: 10.1016/j.bbrc.2014.05.120. Epub 2014 Jun 2.
Glioma glutamate release has been shown to promote the growth of glioma cells and induce neuronal injuries from epilepsy to neuronal death. However, potential counteractions from normal astrocytes against glioma glutamate release have not been fully evaluated. In this study, we investigated the glutamate/glutamine cycling between glioma cells and astrocytes and their impact on neuronal function. Co-cultures of glioma cells with astrocytes (CGA) in direct contact were established under different mix ratio of astrocyte/glioma. Culture medium conditioned in these CGAs were sampled for HPLC measurement, for neuronal ratiometric calcium imaging, and for neuronal survival assay. We found: (1) High levels of glutaminase expression in glioma cells, but not in astrocytes, glutaminase enables glioma cells to release large amount of glutamate in the presence of glutamine. (2) Glutamate levels in CGAs were directly determined by the astrocyte/glioma ratios, indicating a balance between glioma glutamate release and astrocyte glutamate uptake. (3) Culture media from CGAs of higher glioma/astrocyte ratios induced stronger neuronal Ca(2+) response and more severe neuronal death. (4) Co-culturing with astrocytes significantly reduced the growth rate of glioma cells. These results indicate that normal astrocytes in the brain play pivotal roles in glioma growth inhibition and in reducing neuronal injuries from glioma glutamate release. However, as tumor growth, the protective role of astrocytes gradually succumb to glioma cells.
胶质瘤谷氨酸释放已被证明能促进胶质瘤细胞的生长，并导致癫痫到神经元死亡的神经元损伤。然而，正常星形胶质细胞对胶质瘤谷氨酸释放的潜在拮抗作用尚未得到充分评估。在这项研究中，我们研究了胶质瘤细胞和星形胶质细胞之间的谷氨酸/谷氨酰胺循环及其对神经元功能的影响。在不同的星形胶质细胞/胶质瘤混合比例下，建立了胶质瘤细胞与星形胶质细胞（CGA）的直接接触共培养物。从这些 CGAs 中取样培养介质，进行 HPLC 测量、神经元比率钙成像和神经元存活测定。我们发现：（1）在星形胶质细胞中没有表达，而在胶质瘤细胞中高表达谷氨酰胺酶，使胶质瘤细胞在有谷氨酰胺的情况下大量释放谷氨酸。（2）CGAs 中的谷氨酸水平直接由星形胶质细胞/胶质瘤比例决定，表明胶质瘤谷氨酸释放和星形胶质细胞谷氨酸摄取之间存在平衡。（3）较高的星形胶质细胞/胶质瘤比例的 CGAs 培养基诱导更强的神经元 Ca(2+)反应和更严重的神经元死亡。（4）与星形胶质细胞共培养显著降低了胶质瘤细胞的生长速度。这些结果表明，大脑中的正常星形胶质细胞在抑制胶质瘤生长和减少胶质瘤谷氨酸释放引起的神经元损伤方面发挥着关键作用。然而，随着肿瘤的生长，星形胶质细胞的保护作用逐渐被胶质瘤细胞所取代。
