首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Long-term kainic acid exposure reveals compartmentation of glutamate and glutamine metabolism in cultured cerebellar neurons.
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Long-term kainic acid exposure reveals compartmentation of glutamate and glutamine metabolism in cultured cerebellar neurons.

机译:长期的海藻酸暴露表明,在培养的小脑神经元中存在谷氨酸和谷氨酰胺代谢。

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摘要

Glutamate neurotoxicity is implicated in most neurodegenerative diseases, and in the present study the long-term effects of the glutamate agonist kainic acid (KA) on cerebellar neurons are investigated. Primary cell cultures, mainly consisting of glutamatergic granule neurons, were cultured in medium containing 0.05 or 0.50mM KA for 7 days and subsequently incubated in medium containing [U-13C]glutamate or [U-13C]glutamine. The amount of protein and number of cells were greatly reduced in cultures exposed to 0.50 mM KA compared to those exposed to 0.05 mM KA. Glutamine consumption was not affected by KA concentration, whereas that of glutamate was decreased by high KA, confirming reduction in glutamate transport reported earlier. Neurons cultured with 0.50 mM KA and incubated with glutamate contained decreased amounts of glutamate, aspartate and GABA compared to those cultured with 0.05 mM KA. Incubation of cells exposed to 0.50 mM KA with glutamine led to an increased amount of glutamate compared to cells exposed to 0.05 mM KA, whereas the intracellular amounts of aspartate and GABA remained unaffected by KA concentration. Furthermore, mitochondrial metabolism of alpha-[U-13C]ketoglutarate derived from [U-13C]glutamate and [U-13C]glutamine was significantly reduced by 0.50 mM KA. The results presented illustrate differential vulnerability to KA and can only be understood in terms of inter- and intracellular compartmentation.
机译:谷氨酸的神经毒性与大多数神经退行性疾病有关,在本研究中,研究了谷氨酸激动剂海藻酸(KA)对小脑神经元的长期影响。将主要由谷氨酸能颗粒神经元组成的原代细胞培养物在含有0.05或0.50mM KA的培养基中培养7天,然后在含有[U-13C]谷氨酸或[U-13C]谷氨酰胺的培养基中孵育。与暴露于0.05 mM KA的培养相比,暴露于0.50 mM KA的培养物中的蛋白质数量和细胞数量大大减少。谷氨酰胺的消耗不受KA浓度的影响,而谷氨酸的消耗则因高KA而降低,这证实了较早报道的谷氨酸转运减少。与用0.05 mM KA培养的神经元相比,用0.50 mM KA培养并与谷氨酸孵育的神经元所含的谷氨酸,天冬氨酸和GABA含量降低。与暴露于0.05 mM KA的细胞相比,暴露于0.50 mM KA的细胞与谷氨酰胺孵育导致谷氨酸的量增加,而细胞内天冬氨酸和GABA的量不受KA浓度的影响。此外,衍生自[U-13C]谷氨酸和[U-13C]谷氨酰胺的α-[U-13C]酮戊二酸的线粒体代谢显着降低了0.50 mM KA。给出的结果说明了对KA的不同脆弱性,只能从细胞间和细胞内区分开来理解。

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