Taurine release in developing mouse hippocampus is modulated by glutathione and glutathione derivatives.
Taurine release in developing mouse hippocampus is modulated by glutathione and glutathione derivatives.
复制标题
发育中的小鼠海马体中牛磺酸的释放受到谷胱甘肽和谷胱甘肽衍生物的调节。
DOI：
10.1007/s00726-007-0587-z
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发表时间：
2008
期刊：
影响因子：
3.5
通讯作者：
Saransaari,P
中科院分区：
文献类型：
--
作者：
Janáky,R;Shaw,CA;Oja,SS;Saransaari,P
谷胱甘肽（还原型GSH和氧化型GSSG）构成了大脑中对抗氧化应激的重要防御，而牛磺酸是一种抑制性神经调质，特别是在发育中的大脑中。在灌流系统中，研究了GSH、GSSG、甘氨酰甘氨酸、γ-谷氨酰半胱氨酸、半胱氨酰甘氨酸、甘氨酸和半胱氨酸对K+去极化或离子型谷氨酸受体激动剂谷氨酸、红藻氨酸、2-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯（AMPA）和N-甲基-D-天冬氨酸（NMDA）诱发的[~ 3 H]牛磺酸释放的影响。所有的刺激剂（50 mM K+，1 mM谷氨酸，0.1 mM红藻氨酸，0.1 mM AMPA和0.1 mM NMDA）诱发牛磺酸释放受体介导的方式。GSH和GSSG均显著抑制50 mM K+引起的释放。AMPA和谷氨酸诱导的释放也被抑制，而红藻氨酸诱导的释放被GSH和GSSG显著激活。NMDA诱发的释放被证明是最敏感的调制：L-半胱氨酸和甘氨酸以浓度依赖性的方式增强释放，而GSH和GSSG在低（0.1 mM），但不是在较高（1或10 mM）浓度的抑制。γ-谷氨酰半胱氨酸和半胱氨酰甘氨酸可抑制0.1 mM AMPA引起的释放，而甘氨酰甘氨酸则无影响。0.1 mM NMDA诱发的释放被甘氨酰甘氨酸和γ-谷氨酰半胱氨酸抑制。反过来，半胱氨酰甘氨酸在0.1 mM时抑制NMDA诱发的释放，但在1 mM时无活性。谷胱甘肽对牛磺酸释放表现出增强和减弱作用，这取决于谷胱甘肽浓度和所使用的激动剂。谷胱甘肽和牛磺酸作为内源性神经保护效应在出生后早期的生活。
Glutathione (reduced form GSH and oxidized form GSSG) constitutes an important defense against oxidative stress in the brain, and taurine is an inhibitory neuromodulator particularly in the developing brain. The effects of GSH and GSSG and glycylglycine, γ-glutamylcysteine, cysteinylglycine, glycine and cysteine on the release of [3H]taurine evoked by K+-depolarization or the ionotropic glutamate receptor agonists glutamate, kainate, 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) andN-methyl-D-aspartate (NMDA) were now studied in slices from the hippocampi from 7-day-old mouse pups in a perfusion system. All stimulatory agents (50 mM K+, 1 mM glutamate, 0.1 mM kainate, 0.1 mM AMPA and 0.1 mM NMDA) evoked taurine release in a receptor-mediated manner. Both GSH and GSSG significantly inhibited the release evoked by 50 mM K+. The release induced by AMPA and glutamate was also inhibited, while the kainate-evoked release was significantly activated by both GSH and GSSG. The NMDA-evoked release proved the most sensitive to modulation: L-Cysteine and glycine enhanced the release in a concentration-dependent manner, whereas GSH and GSSG were inhibitory at low (0.1 mM) but not at higher (1 or 10 mM) concentrations. The release evoked by 0.1 mM AMPA was inhibited by γ-glutamylcysteine and cysteinylglycine, whereas glycylglycine had no effect. The 0.1 mM NMDA-evoked release was inhibited by glycylglycine and γ-glutamylcysteine. In turn, cysteinylglycine inhibited the NMDA-evoked release at 0.1 mM, but was inactive at 1 mM. Glutathione exhibited both enhancing and attenuating effects on taurine release, depending on the glutathione concentration and on the agonist used. Both glutathione and taurine act as endogenous neuroprotective effectors during early postnatal life.