Laboratório de Neuroendocrinologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Campus do Guamá, Av. Augusto Corrêa, 01, Belém, Pará, 66075-900, Brazil.
Neurochem Res. 2011 Mar;36(3):412-8. doi: 10.1007/s11064-010-0356-3. Epub 2010 Dec 16.
This study was undertaken in order to characterize the role of the glutamate/aspartate transporter (GLAST) in the glutathione (GSH) efflux induced by glutamate. Our results demonstrated that retinal cell cultures exhibit two mechanisms of GSH release, one Na(+)-independent and other Na(+)-dependent. Glutamate and aspartate induced GSH efflux only in presence of Na(+). Treatment with PCD (L-trans-Pyrrolidine-2,4-dicarboxylate), a transportable glutamate uptake blocker, increased GSH release indicating that GSH can be carried by glutamate transporters in retinal cell cultures. Added to this, treatment with zinc ion cultures, a recognized inhibitor of GLAST blocked GSH efflux evoked by glutamate. Treatment with NMDA antagonist (MK-801) did not have any effect on the GSH release induced by glutamate. These results suggest that glutamate induces GLAST-mediated release of GSH from retinal cell cultures and this could represent an important mechanism of cellular protection against glutamate toxicity in the CNS.
本研究旨在探讨谷氨酸/天冬氨酸转运体（GLAST）在谷氨酸诱导的谷胱甘肽（GSH）外排中的作用。我们的结果表明，视网膜细胞培养物存在两种 GSH 释放机制，一种是不依赖于 Na+的，另一种是依赖于 Na+的。谷氨酸和天冬氨酸仅在存在 Na+的情况下诱导 GSH 外排。用 PCD（L-转吡咯烷-2,4-二羧酸酯）处理，一种可转运的谷氨酸摄取阻断剂，增加了 GSH 的释放，表明 GSH 可以通过谷氨酸转运体在视网膜细胞培养物中转运。此外，用锌离子处理，一种公认的 GLAST 抑制剂，阻断了谷氨酸诱导的 GSH 外排。用 NMDA 拮抗剂（MK-801）处理对谷氨酸诱导的 GSH 释放没有任何影响。这些结果表明，谷氨酸诱导 GLAST 介导的视网膜细胞培养物中 GSH 的释放，这可能是中枢神经系统中对抗谷氨酸毒性的一种重要细胞保护机制。
