Glutathione is a physiologic reservoir of neuronal glutamate.
Glutathione is a physiologic reservoir of neuronal glutamate.
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DOI：
10.1016/j.bbrc.2011.04.087
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发表时间：
2011-06-17
影响因子：
3.1
通讯作者：
Sedlak, Thomas W.
中科院分区：
文献类型：
--
作者：
Koga, Minori;Serritella, Anthony V.;Messmer, Marcus M.;Hayashi-Takagi, Akiko;Hester, Lynda D.;Snyder, Solomon H.;Sawa, Akira;Sedlak, Thomas W.
谷氨酸是大脑的主要兴奋性神经递质，参与多种生理和病理过程，包括学习和记忆。谷胱甘肽是一种由谷氨酸、半胱氨酸和甘氨酸组成的三肽，在抗氧化防御和药物解毒中发挥重要的辅助因子作用，但谷胱甘肽缺陷发生在多种神经精神疾病中。谷胱甘肽的合成和代谢由酶循环（γ-谷氨酰循环）控制，可以实现细胞内谷胱甘肽浓度为 1-10 毫摩尔。由于大脑中谷胱甘肽的数量相当大且周转速度快，我们假设谷胱甘肽可能作为神经谷氨酸的储存库。在用针对谷胱甘肽代谢循环的三种不同酶的分子抑制剂治疗后，我们对 HT22 海马神经元、PC12 细胞和初级皮质神经元中的谷氨酸进行了定量。抑制 5-氧代脯氨酸酶和 γ-谷氨酰转移酶（从谷胱甘肽中释放谷氨酸的酶）会导致谷氨酸减少。相反，抑制γ-谷氨酰半胱氨酸连接酶（利用谷氨酸合成谷胱甘肽）会导致大量谷氨酸积累。抑制谷胱甘肽合成后谷氨酸水平的增加暂时先于氧化应激的后续影响。
Glutamate, the principal excitatory neurotransmitter of the brain, participates in a multitude of physiologic and pathologic processes, including learning and memory. Glutathione, a tripeptide composed of the amino acids glutamate, cysteine, and glycine, serves important cofactor roles in antioxidant defense and drug detoxification, but glutathione deficits occur in multiple neuropsychiatric disorders. Glutathione synthesis and metabolism are governed by a cycle of enzymes, the γ-glutamyl cycle, which can achieve intracellular glutathione concentrations of 1-10 millimolar. Because of the considerable quantity of brain glutathione and its rapid turnover, we hypothesized that glutathione may serve as a reservoir of neural glutamate. We quantified glutamate in HT22 hippocampal neurons, PC12 cells and primary cortical neurons after treatment with molecular inhibitors targeting three different enzymes of the glutathione metabolic cycle. Inhibiting 5-oxoprolinase and γ-glutamyl transferase, enzymes that liberate glutamate from glutathione, leads to decreases in glutamate. In contrast, inhibition of γ-glutamyl cysteine ligase, which uses glutamate to synthesize glutathione, results in substantial glutamate accumulation. Increased glutamate levels following inhibition of glutathione synthesis temporally precede later effects upon oxidative stress.
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影响因子：
16.2
作者：
Ishikawa, T;Sahara, Y;Takahashi, T
通讯作者：
Takahashi, T
影响因子：
10.6
作者：
Forman, Henry Jay;Zhang, Hongqiao;Rinna, Alessandra
通讯作者：
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影响因子：
1.4
作者：
Liguz-Lecznar, Monika;Skangiel-Kramska, Jolanta
通讯作者：
Skangiel-Kramska, Jolanta
影响因子：
2.9
作者：
HAMBERGER, AC;CHIANG, GH;COTMAN, CW
通讯作者：
COTMAN, CW
影响因子：
6.2
作者：
Chapman, J;Zhou, MJ
通讯作者：
Zhou, MJ