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Methylglyoxal Induces Changes in the Glyoxalase System and Impairs Glutamate Uptake Activity in Primary Astrocytes
The impairment of astrocyte functions is associated with diabetes mellitus and other neurodegenerative diseases. Astrocytes have been proposed to be essential cells for neuroprotection against elevated levels of methylglyoxal (MG), a highly reactive aldehyde derived from the glycolytic pathway. MG e...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480050/ https://www.ncbi.nlm.nih.gov/pubmed/28685011 http://dx.doi.org/10.1155/2017/9574201 |
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author | Hansen, Fernanda Galland, Fabiana Lirio, Franciane de Souza, Daniela Fraga Da Ré, Carollina Pacheco, Rafaela Ferreira Vizuete, Adriana Fernanda Quincozes-Santos, André Leite, Marina Concli Gonçalves, Carlos-Alberto |
author_facet | Hansen, Fernanda Galland, Fabiana Lirio, Franciane de Souza, Daniela Fraga Da Ré, Carollina Pacheco, Rafaela Ferreira Vizuete, Adriana Fernanda Quincozes-Santos, André Leite, Marina Concli Gonçalves, Carlos-Alberto |
author_sort | Hansen, Fernanda |
collection | PubMed |
description | The impairment of astrocyte functions is associated with diabetes mellitus and other neurodegenerative diseases. Astrocytes have been proposed to be essential cells for neuroprotection against elevated levels of methylglyoxal (MG), a highly reactive aldehyde derived from the glycolytic pathway. MG exposure impairs primary astrocyte viability, as evaluated by different assays, and these cells respond to MG elevation by increasing glyoxalase 1 activity and glutathione levels, which improve cell viability and survival. However, C6 glioma cells have shown strong signs of resistance against MG, without significant changes in the glyoxalase system. Results for aminoguanidine coincubation support the idea that MG toxicity is mediated by glycation. We found a significant decrease in glutamate uptake by astrocytes, without changes in the expression of the major transporters. Carbenoxolone, a nonspecific inhibitor of gap junctions, prevented the cytotoxicity induced by MG in astrocyte cultures. Thus, our data reinforce the idea that astrocyte viability depends on gap junctions and that the impairment induced by MG involves glutamate excitotoxicity. The astrocyte susceptibility to MG emphasizes the importance of this compound in neurodegenerative diseases, where the neuronal damage induced by MG may be aggravated by the commitment of the cells charged with MG clearance. |
format | Online Article Text |
id | pubmed-5480050 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-54800502017-07-06 Methylglyoxal Induces Changes in the Glyoxalase System and Impairs Glutamate Uptake Activity in Primary Astrocytes Hansen, Fernanda Galland, Fabiana Lirio, Franciane de Souza, Daniela Fraga Da Ré, Carollina Pacheco, Rafaela Ferreira Vizuete, Adriana Fernanda Quincozes-Santos, André Leite, Marina Concli Gonçalves, Carlos-Alberto Oxid Med Cell Longev Research Article The impairment of astrocyte functions is associated with diabetes mellitus and other neurodegenerative diseases. Astrocytes have been proposed to be essential cells for neuroprotection against elevated levels of methylglyoxal (MG), a highly reactive aldehyde derived from the glycolytic pathway. MG exposure impairs primary astrocyte viability, as evaluated by different assays, and these cells respond to MG elevation by increasing glyoxalase 1 activity and glutathione levels, which improve cell viability and survival. However, C6 glioma cells have shown strong signs of resistance against MG, without significant changes in the glyoxalase system. Results for aminoguanidine coincubation support the idea that MG toxicity is mediated by glycation. We found a significant decrease in glutamate uptake by astrocytes, without changes in the expression of the major transporters. Carbenoxolone, a nonspecific inhibitor of gap junctions, prevented the cytotoxicity induced by MG in astrocyte cultures. Thus, our data reinforce the idea that astrocyte viability depends on gap junctions and that the impairment induced by MG involves glutamate excitotoxicity. The astrocyte susceptibility to MG emphasizes the importance of this compound in neurodegenerative diseases, where the neuronal damage induced by MG may be aggravated by the commitment of the cells charged with MG clearance. Hindawi 2017 2017-06-08 /pmc/articles/PMC5480050/ /pubmed/28685011 http://dx.doi.org/10.1155/2017/9574201 Text en Copyright © 2017 Fernanda Hansen et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Hansen, Fernanda Galland, Fabiana Lirio, Franciane de Souza, Daniela Fraga Da Ré, Carollina Pacheco, Rafaela Ferreira Vizuete, Adriana Fernanda Quincozes-Santos, André Leite, Marina Concli Gonçalves, Carlos-Alberto Methylglyoxal Induces Changes in the Glyoxalase System and Impairs Glutamate Uptake Activity in Primary Astrocytes |
title | Methylglyoxal Induces Changes in the Glyoxalase System and Impairs Glutamate Uptake Activity in Primary Astrocytes |
title_full | Methylglyoxal Induces Changes in the Glyoxalase System and Impairs Glutamate Uptake Activity in Primary Astrocytes |
title_fullStr | Methylglyoxal Induces Changes in the Glyoxalase System and Impairs Glutamate Uptake Activity in Primary Astrocytes |
title_full_unstemmed | Methylglyoxal Induces Changes in the Glyoxalase System and Impairs Glutamate Uptake Activity in Primary Astrocytes |
title_short | Methylglyoxal Induces Changes in the Glyoxalase System and Impairs Glutamate Uptake Activity in Primary Astrocytes |
title_sort | methylglyoxal induces changes in the glyoxalase system and impairs glutamate uptake activity in primary astrocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480050/ https://www.ncbi.nlm.nih.gov/pubmed/28685011 http://dx.doi.org/10.1155/2017/9574201 |
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