Glutamine as an energy substrate in cultured neurons during glucose deprivation
Glutamine as an energy substrate in cultured neurons during glucose deprivation
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DOI：
10.1002/jnr.21262
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发表时间：
2007-11-15
影响因子：
4.2
通讯作者：
Hertz, Leif
中科院分区：
文献类型：
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作者：
Peng, Liang;Gu, Li;Hertz, Leif
在葡萄糖剥夺过程中，在不同的脑制备物中，包括突触体和培养的星形胶质细胞中观察到谷氨酰胺形成天冬氨酸的增加。这种提供大量能量的反应在不同类型的神经元中发生的程度尚不清楚。目前的研究表明，（CO2）-C-14形成[U-C-14]谷氨酰胺在小脑颗粒神经元，一种谷氨酸能制剂，增加了60%，在葡萄糖剥夺，表明增强天冬氨酸形成或增加谷氨酰胺的完全氧化降解。在皮层中间神经元（GABAergiC制剂）的原代培养物中，[U-C-14]谷氨酰胺产生（CO2）-C-14的速率低4倍，并且不受葡萄糖剥夺的刺激。在以谷氨酰胺（0.8 mM）作为唯一代谢底物的孵育期间，小脑颗粒细胞维持12 nmol/min/mg蛋白质的耗氧速率，对应于8 nmol/min/mg蛋白质的天冬氨酸形成（谷氨酰胺和天冬氨酸之间发生三次氧化）或3 nmol/min/mg蛋白质的总氧化降解。在葡萄糖剥夺期间，天冬氨酸形成的速率增加，并且在磷酸盐缓冲盐水中孵育20分钟期间，在0.2 mM谷氨酰胺下，天冬氨酸形成的速率达到3.3 nmol/min/mg蛋白质，如果在0.8 mM谷氨酰胺下测量，则可能更多。这些值与基于耗氧量计算的谷氨酰胺利用率一致，并且存在一些谷氨酰胺完全氧化降解的可能性，正如其他作者基于小脑颗粒神经元中天冬氨酸的丙酮酸再循环和乳酸标记所示。(C)2007 Wiley-Liss，Inc.
During glucose deprivation an increase in aspartate formation from glutamine has been observed in different brain preparations, including synaptosomes and cultured astrocytes. To what extent this reaction, which provides a substantial amount of energy, occurs in different types of neurons is unknown. The present study shows that (CO2)-C-14 formation from [U-C-14]glutamine in cerebellar granule neurons, a glutamatergic preparation, increased by 60% during glucose deprivation, indicating enhanced aspartate formation or increased complete oxidative degradation of glutamine. In primary cultures of cerebrocortical interneurons, a GABAergiC preparation, the rate of (CO2)-C-14 production from [U-C-14] glutamine was four times lower and not stimulated by glucose deprivation. During incubation with glutamine (0.8 mM) as the only metabolic substrate, cerebellar granule cells maintained an oxygen consumption rate of 12 nmol/min/mg protein, corresponding to an aspartate formation of 8 nmol/min/mg protein (three oxidations occur between glutamine and aspartate) or to a total oxidative degradation of 3 nmol/min/mg protein. During glucose deprivation, the rate of aspartate formation increased, and during a 20-min incubation in phosphate-buffered saline it amounted to 3.3 nmol/min/mg protein at 0.2 mM glutamine, which might have been more if measured at 0.8 mM glutamine. These values are consistent with the rate of glutamine utilization calculated based on oxygen consumption and leaves open the possibility that some glutamine is completely degraded oxidatively, as has been shown by other authors based on pyruvate recycling and labeling of lactate from aspartate in cerebellar granule neurons. (C) 2007 Wiley-Liss, Inc.