Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity
Autor(a) principal: | |
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Data de Publicação: | 2007 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Medical and Biological Research |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000300001 |
Resumo: | This review addresses the mechanisms of methylmercury (MeHg)-induced neurotoxicity, specifically examining the role of oxidative stress in mediating neuronal damage. A number of critical findings point to a central role for astrocytes in mediating MeHg-induced neurotoxicity as evidenced by the following observations: a) MeHg preferentially accumulates in astrocytes; b) MeHg specifically inhibits glutamate uptake in astrocytes; c) neuronal dysfunction is secondary to disturbances in astrocytes. The generation of reactive oxygen species (ROS) by MeHg has been observed in various experimental paradigms. For example, MeHg enhances ROS formation both in vivo (rodent cerebellum) and in vitro (isolated rat brain synaptosomes), as well as in neuronal and mixed reaggregating cell cultures. Antioxidants, including selenocompounds, can rescue astrocytes from MeHg-induced cytotoxicity by reducing ROS formation. We emphasize that oxidative stress plays a significant role in mediating MeHg-induced neurotoxic damage with active involvement of the mitochondria in this process. Furthermore, we provide a mechanistic overview on oxidative stress induced by MeHg that is triggered by a series of molecular events such as activation of various kinases, stress proteins and other immediate early genes culminating in cell damage. |
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Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicityMethylmercury neurotoxicityOxidative stressGlutamate and selenocompoundsReactive oxygen speciesAstrocytesThis review addresses the mechanisms of methylmercury (MeHg)-induced neurotoxicity, specifically examining the role of oxidative stress in mediating neuronal damage. A number of critical findings point to a central role for astrocytes in mediating MeHg-induced neurotoxicity as evidenced by the following observations: a) MeHg preferentially accumulates in astrocytes; b) MeHg specifically inhibits glutamate uptake in astrocytes; c) neuronal dysfunction is secondary to disturbances in astrocytes. The generation of reactive oxygen species (ROS) by MeHg has been observed in various experimental paradigms. For example, MeHg enhances ROS formation both in vivo (rodent cerebellum) and in vitro (isolated rat brain synaptosomes), as well as in neuronal and mixed reaggregating cell cultures. Antioxidants, including selenocompounds, can rescue astrocytes from MeHg-induced cytotoxicity by reducing ROS formation. We emphasize that oxidative stress plays a significant role in mediating MeHg-induced neurotoxic damage with active involvement of the mitochondria in this process. Furthermore, we provide a mechanistic overview on oxidative stress induced by MeHg that is triggered by a series of molecular events such as activation of various kinases, stress proteins and other immediate early genes culminating in cell damage.Associação Brasileira de Divulgação Científica2007-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000300001Brazilian Journal of Medical and Biological Research v.40 n.3 2007reponame:Brazilian Journal of Medical and Biological Researchinstname:Associação Brasileira de Divulgação Científica (ABDC)instacron:ABDC10.1590/S0100-879X2007000300001info:eu-repo/semantics/openAccessAschner,M.Syversen,T.Souza,D.O.Rocha,J.B.T.Farina,M.eng2008-02-12T00:00:00Zoai:scielo:S0100-879X2007000300001Revistahttps://www.bjournal.org/https://old.scielo.br/oai/scielo-oai.phpbjournal@terra.com.br||bjournal@terra.com.br1414-431X0100-879Xopendoar:2008-02-12T00:00Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC)false |
dc.title.none.fl_str_mv |
Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity |
title |
Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity |
spellingShingle |
Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity Aschner,M. Methylmercury neurotoxicity Oxidative stress Glutamate and selenocompounds Reactive oxygen species Astrocytes |
title_short |
Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity |
title_full |
Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity |
title_fullStr |
Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity |
title_full_unstemmed |
Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity |
title_sort |
Involvement of glutamate and reactive oxygen species in methylmercury neurotoxicity |
author |
Aschner,M. |
author_facet |
Aschner,M. Syversen,T. Souza,D.O. Rocha,J.B.T. Farina,M. |
author_role |
author |
author2 |
Syversen,T. Souza,D.O. Rocha,J.B.T. Farina,M. |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Aschner,M. Syversen,T. Souza,D.O. Rocha,J.B.T. Farina,M. |
dc.subject.por.fl_str_mv |
Methylmercury neurotoxicity Oxidative stress Glutamate and selenocompounds Reactive oxygen species Astrocytes |
topic |
Methylmercury neurotoxicity Oxidative stress Glutamate and selenocompounds Reactive oxygen species Astrocytes |
description |
This review addresses the mechanisms of methylmercury (MeHg)-induced neurotoxicity, specifically examining the role of oxidative stress in mediating neuronal damage. A number of critical findings point to a central role for astrocytes in mediating MeHg-induced neurotoxicity as evidenced by the following observations: a) MeHg preferentially accumulates in astrocytes; b) MeHg specifically inhibits glutamate uptake in astrocytes; c) neuronal dysfunction is secondary to disturbances in astrocytes. The generation of reactive oxygen species (ROS) by MeHg has been observed in various experimental paradigms. For example, MeHg enhances ROS formation both in vivo (rodent cerebellum) and in vitro (isolated rat brain synaptosomes), as well as in neuronal and mixed reaggregating cell cultures. Antioxidants, including selenocompounds, can rescue astrocytes from MeHg-induced cytotoxicity by reducing ROS formation. We emphasize that oxidative stress plays a significant role in mediating MeHg-induced neurotoxic damage with active involvement of the mitochondria in this process. Furthermore, we provide a mechanistic overview on oxidative stress induced by MeHg that is triggered by a series of molecular events such as activation of various kinases, stress proteins and other immediate early genes culminating in cell damage. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-03-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000300001 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2007000300001 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/S0100-879X2007000300001 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
publisher.none.fl_str_mv |
Associação Brasileira de Divulgação Científica |
dc.source.none.fl_str_mv |
Brazilian Journal of Medical and Biological Research v.40 n.3 2007 reponame:Brazilian Journal of Medical and Biological Research instname:Associação Brasileira de Divulgação Científica (ABDC) instacron:ABDC |
instname_str |
Associação Brasileira de Divulgação Científica (ABDC) |
instacron_str |
ABDC |
institution |
ABDC |
reponame_str |
Brazilian Journal of Medical and Biological Research |
collection |
Brazilian Journal of Medical and Biological Research |
repository.name.fl_str_mv |
Brazilian Journal of Medical and Biological Research - Associação Brasileira de Divulgação Científica (ABDC) |
repository.mail.fl_str_mv |
bjournal@terra.com.br||bjournal@terra.com.br |
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1754302935608590336 |