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Evidence of glutathione transporter in rat brain synaptosomal membrane vesicles.

机译:大鼠脑突触体膜囊泡中谷胱甘肽转运蛋白的证据。

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摘要

Glutathione (GSH) transport was studied in synaptosomal membrane vesicles (SMV) of rat cerebral cortex. The present study shows that GSH uptake into SMV occurs very quickly in a time-dependent manner into an osmotically active intravesicular space. The initial rate of transport followed Michealis-Menten saturation kinetics with a Km 4.5+/-0.8 microM that shows a high affinity of the transporter for GSH. Therefore GSH uptake in SMV occurs by a mediated transport system which can be activated by either an inward gradient of cations, like Na+ or K+, or membrane depolarization. These results, together with those obtained by valinomycin-induced K+ diffusion potential, indicate that GSH synaptosomal transport is electrogenic by a negative charge transfer. The increase of GSH uptake measured by trans-stimulation experiments confirms a GSH bidirectional mediated transport which seems susceptible of modulation by changes in ionic fluxes and in the membrane potential. These results may indicate a possible involvement of this transporter in the role suggested for GSH in synaptic neurotransmission; also considering that GSH precursor of neuroactive aminoacids (glycine, glutamate), may contribute to regulate their level in synapses. Finally, a GSH transporter in synaptosomes may contribute to maintaining the GSH homeostasis in cerebral cortex, where decreases of GSH levels have been related to susceptibility to neuropathologies.
机译:谷胱甘肽(GSH)转运在大鼠大脑皮层的突触体膜囊泡(SMV)中进行了研究。本研究表明,GSH吸收入SMV的时间呈时间依赖性,并迅速进入渗透性囊泡内。初始转运速率遵循米迦勒-门腾饱和动力学,Km 4.5 +/- 0.8 microM,表明转运蛋白对GSH的亲和力高。因此,SMV中GSH的吸收是通过介导的转运系统发生的,该转运系统可以通过阳离子的内向梯度(如Na +或K +)或膜去极化来激活。这些结果,与通过缬氨霉素诱导的K +扩散势获得的结果一起,表明GSH突触体转运是通过负电荷转移产生的。通过反式刺激实验测得的GSH摄取量的增加证实了GSH双向介导的转运,似乎易于受到离子通量和膜电位变化的调节。这些结果可能表明该转运蛋白可能参与了GSH在突触神经传递中的作用。还考虑到神经活性氨基酸的GSH前体(甘氨酸,谷氨酸)可能有助于调节突触中的水平。最后,突触小体中的GSH转运蛋白可能有助于维持大脑皮层中GSH的体内稳态,其中GSH含量的下降与神经病理学的易感性有关。

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