Department of Neuroscience, Jordan University of Science and Technology (JUST), Irbid, 22110, Jordan.
Neurochem Res. 2011 Aug;36(8):1566-73. doi: 10.1007/s11064-011-0485-3. Epub 2011 May 3.
This study was undertaken to determine if the ketogenic diet could be useful for glioblastoma patients. The hypothesis tested was whether glioblastoma cells can metabolize ketone bodies. Cerebellar astrocytes and C6 glioblastoma cells were incubated in glutamine and serum free medium containing [2,4-(13)C]β-hydroxybutyrate (BHB) with and without glucose. Furthermore, C6 cells were incubated with [1-(13)C]glucose in the presence and absence of BHB. Cell extracts were analyzed by mass spectrometry and media by (1)H magnetic resonance spectroscopy and HPLC. Using [2,4-(13)C]BHB and [1-(13)C]glucose it could be shown that C6 cells, in analogy to astrocytes, had efficient mitochondrial activity, evidenced by (13)C labeling of glutamate, glutamine and aspartate. However, in the presence of glucose, astrocytes were able to produce and release glutamine, whereas this was not accomplished by the C6 cells, suggesting lack of anaplerosis in the latter. We hypothesize that glioblastoma cells kill neurons by not supplying the necessary glutamine, and by releasing glutamate.
本研究旨在确定生酮饮食是否对胶质母细胞瘤患者有用。测试的假设是胶质母细胞瘤细胞是否可以代谢酮体。小脑星形胶质细胞和 C6 胶质母细胞瘤细胞在含有[2,4-(13)C]β-羟基丁酸（BHB）的无谷氨酰胺和无血清培养基中孵育，有或没有葡萄糖。此外，C6 细胞在存在和不存在 BHB 的情况下用[1-(13)C]葡萄糖孵育。通过质谱法分析细胞提取物，通过(1)H 磁共振波谱法和 HPLC 分析培养基。使用[2,4-(13)C]BHB 和[1-(13)C]葡萄糖，可以证明 C6 细胞与星形胶质细胞一样具有高效的线粒体活性，这表现在谷氨酸、谷氨酰胺和天冬氨酸的(13)C 标记上。然而，在葡萄糖存在的情况下，星形胶质细胞能够产生和释放谷氨酰胺，而 C6 细胞则不能，这表明后者缺乏氨酰化作用。我们假设胶质母细胞瘤细胞通过不提供必需的谷氨酰胺和释放谷氨酸来杀死神经元。
