Glutamate/glutamine metabolism coupling between astrocytes and glioma cells: neuroprotection and inhibition of glioma growth.
Glutamate/glutamine metabolism coupling between astrocytes and glioma cells: neuroprotection and inhibition of glioma growth.
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星形胶质细胞和神经胶质瘤细胞之间的谷氨酸/谷氨酰胺代谢耦合：神经保护和神经胶质瘤生长的抑制。
DOI：
10.1016/j.bbrc.2014.05.120
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发表时间：
2014
影响因子：
3.1
通讯作者：
Z. Ye
中科院分区：
文献类型：
--
作者：
P. Yao;D. Kang;Ru;Bing Ye;Wei Wang;Z. Ye
神经胶质瘤谷氨酸释放已被证明可促进神经胶质瘤细胞的生长并诱导从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神经胶质瘤谷氨酸释放的潜在对抗作用尚未得到充分评估。在这项研究中，我们研究了谷氨酸/谷氨酰胺在胶质瘤细胞和星形胶质细胞之间的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直接接触的共培养。在这些CGAs条件下的培养基取样进行HPLC测量，神经元比例钙成像和神经元存活测定。我们发现：(1)谷氨酰胺酶在胶质瘤细胞中高水平表达，而在星形胶质细胞中不表达，谷氨酰胺酶使胶质瘤细胞在谷氨酰胺存在的情况下释放大量谷氨酸。(2) CGAs中谷氨酸水平直接由星形胶质细胞/胶质瘤比值决定，表明胶质瘤谷氨酸释放与星形胶质细胞谷氨酸摄取之间存在平衡。(3)高胶质瘤/星形胶质细胞比例的CGAs培养基诱导更强的神经元Ca2+反应和更严重的神经元死亡。(4)与星形胶质细胞共培养可显著降低胶质瘤细胞的生长速度。这些结果表明，脑内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中起关键作用。然而，随着肿瘤的生长，星形胶质细胞的保护作用逐渐屈服于胶质瘤细胞。
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 Ca2+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.
影响因子：
11.2
作者：
Lyons, Susan A.;Chung, W. Joon;Sontheimer, Harald
通讯作者：
Sontheimer, Harald
癌基因 AEG-1 通过增加谷氨酸兴奋毒性来促进神经胶质瘤诱导的神经变性。
影响因子：
11.2
作者：
Lee SG;Kim K;Kegelman TP;Dash R;Das SK;Choi JK;Emdad L;Howlett EL;Jeon HY;Su ZZ;Yoo BK;Sarkar D;Kim SH;Kang DC;Fisher PB
通讯作者：
Fisher PB