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Glutamate Induces Glutathione Efflux Mediated by Glutamate/Aspartate Transporter in Retinal Cell Cultures

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Abstract

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.

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Abbreviations

BSA:

Bovine serum albumin

DMEM:

Dulbecco’s modified Eagle’s medium

DTNB:

5,5,8-dithiobis-2-nitrobenzoic acid

FBS:

Fetal bovine serum

GLAST:

Glutamate-aspartate transporter

MK-801:

(5R,2S)-(1)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate

PDC:

L-trans-Pyrrolidine-2,4-dicarboxylate

TNB:

Nitrobenzoic acid

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Acknowledgments

We would like to thank Makarú LTDA for supplying chicken eggs used in this work. This project was financially supported by CNPq and FAPESPA.

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Authors and Affiliations

  1. Laboratório de Neuroendocrinologia, Instituto de Ciências Biológicas, Universidade Federal do Pará, Campus do Guamá, Av. Augusto Corrêa, 01, Belém, Pará, 66075-900, Brazil

    T. B. Garcia, D. L. W. Picanço-Diniz & A. M. Herculano

  2. Laboratório de Neuroquímica Molecular e Celular, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brazil

    K. R. M. Oliveira, J. L. M. do Nascimento & T. C. Mota

  3. Laboratório de Farmacologia Molecular; Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, Pará, Brazil

    M. E. Crespo-López

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  1. T. B. Garcia
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  2. K. R. M. Oliveira
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  3. J. L. M. do Nascimento
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Correspondence to A. M. Herculano.

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Garcia, T.B., Oliveira, K.R.M., do Nascimento, J.L.M. et al. Glutamate Induces Glutathione Efflux Mediated by Glutamate/Aspartate Transporter in Retinal Cell Cultures. Neurochem Res 36, 412–418 (2011). https://doi.org/10.1007/s11064-010-0356-3

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