Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathways
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/136216 |
Resumo: | Ascorbate, the reduced form of Vitamin C, is one of the most abundant and important low-molecular weight antioxidants in living tissues. Most animals synthesize Vitamin C, but some primates, including humans, have lost this capacity due to disruption in L-gulono-gamma-lactone oxidase gene. Because of this incapacity, those animals must obtain Vitamin C from the diet. Ascorbate is highly concentrated in the central nervous system (CNS), including the retina, and plays essential roles in neuronal physiology. Ascorbate transport into cells is controlled by Sodium Vitamin C Co-Transporters (SVCTs). There are four SVCT isoforms and SVCT2 is the major isoform controlling ascorbate transport in the CNS. Regarding ascorbate release from retinal neurons, Glutamate, by activating its ionotropic receptors leads to ascorbate release via the reversion of SVCT2. Moreover, dopamine, via activation of D1 receptor/cyclic AMP/EPAC2 pathway, also induces ascorbate release via SVCT2 reversion. Because the dopaminergic and glutamatergic systems are interconnected in the CNS, we hypothesized that dopamine could regulate ascorbate release indirectly, via the glutamatergic system. Here we reveal that dopamine increases the release of D-Aspartate from retinal neurons in a way independent on calcium ions and dependent on excitatory amino acid transporters. In addition, dopamine-dependent SVCT2 reversion leading to ascorbate release occurs by activation of AMPA/Kainate receptors and downstream ERK/AKT pathways. Overall, our data reveal a dopamine-to-glutamate signaling that regulates the bioavailability of ascorbate in neuronal cells. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathwaysAktD-aspartateD1rEpacErkExcitatory amino acid transportersSvct2Vitamin CAscorbate, the reduced form of Vitamin C, is one of the most abundant and important low-molecular weight antioxidants in living tissues. Most animals synthesize Vitamin C, but some primates, including humans, have lost this capacity due to disruption in L-gulono-gamma-lactone oxidase gene. Because of this incapacity, those animals must obtain Vitamin C from the diet. Ascorbate is highly concentrated in the central nervous system (CNS), including the retina, and plays essential roles in neuronal physiology. Ascorbate transport into cells is controlled by Sodium Vitamin C Co-Transporters (SVCTs). There are four SVCT isoforms and SVCT2 is the major isoform controlling ascorbate transport in the CNS. Regarding ascorbate release from retinal neurons, Glutamate, by activating its ionotropic receptors leads to ascorbate release via the reversion of SVCT2. Moreover, dopamine, via activation of D1 receptor/cyclic AMP/EPAC2 pathway, also induces ascorbate release via SVCT2 reversion. Because the dopaminergic and glutamatergic systems are interconnected in the CNS, we hypothesized that dopamine could regulate ascorbate release indirectly, via the glutamatergic system. Here we reveal that dopamine increases the release of D-Aspartate from retinal neurons in a way independent on calcium ions and dependent on excitatory amino acid transporters. In addition, dopamine-dependent SVCT2 reversion leading to ascorbate release occurs by activation of AMPA/Kainate receptors and downstream ERK/AKT pathways. Overall, our data reveal a dopamine-to-glutamate signaling that regulates the bioavailability of ascorbate in neuronal cells.Frontiers Media20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/136216eng1662-454810.3389/fnins.2019.00453Portugal, CCEncarnação, TGDomith, IRodrigues, ASOliveira, NASocodato, RPaes-de-carvalho, Rinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-26T14:19:28ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathways |
title |
Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathways |
spellingShingle |
Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathways Portugal, CC Akt D-aspartate D1r Epac Erk Excitatory amino acid transporters Svct2 Vitamin C |
title_short |
Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathways |
title_full |
Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathways |
title_fullStr |
Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathways |
title_full_unstemmed |
Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathways |
title_sort |
Dopamine-induced ascorbate release from retinal neurons involves glutamate release, activation of AMPA/Kainate receptors and downstream signaling pathways |
author |
Portugal, CC |
author_facet |
Portugal, CC Encarnação, TG Domith, I Rodrigues, AS Oliveira, NA Socodato, R Paes-de-carvalho, R |
author_role |
author |
author2 |
Encarnação, TG Domith, I Rodrigues, AS Oliveira, NA Socodato, R Paes-de-carvalho, R |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Portugal, CC Encarnação, TG Domith, I Rodrigues, AS Oliveira, NA Socodato, R Paes-de-carvalho, R |
dc.subject.por.fl_str_mv |
Akt D-aspartate D1r Epac Erk Excitatory amino acid transporters Svct2 Vitamin C |
topic |
Akt D-aspartate D1r Epac Erk Excitatory amino acid transporters Svct2 Vitamin C |
description |
Ascorbate, the reduced form of Vitamin C, is one of the most abundant and important low-molecular weight antioxidants in living tissues. Most animals synthesize Vitamin C, but some primates, including humans, have lost this capacity due to disruption in L-gulono-gamma-lactone oxidase gene. Because of this incapacity, those animals must obtain Vitamin C from the diet. Ascorbate is highly concentrated in the central nervous system (CNS), including the retina, and plays essential roles in neuronal physiology. Ascorbate transport into cells is controlled by Sodium Vitamin C Co-Transporters (SVCTs). There are four SVCT isoforms and SVCT2 is the major isoform controlling ascorbate transport in the CNS. Regarding ascorbate release from retinal neurons, Glutamate, by activating its ionotropic receptors leads to ascorbate release via the reversion of SVCT2. Moreover, dopamine, via activation of D1 receptor/cyclic AMP/EPAC2 pathway, also induces ascorbate release via SVCT2 reversion. Because the dopaminergic and glutamatergic systems are interconnected in the CNS, we hypothesized that dopamine could regulate ascorbate release indirectly, via the glutamatergic system. Here we reveal that dopamine increases the release of D-Aspartate from retinal neurons in a way independent on calcium ions and dependent on excitatory amino acid transporters. In addition, dopamine-dependent SVCT2 reversion leading to ascorbate release occurs by activation of AMPA/Kainate receptors and downstream ERK/AKT pathways. Overall, our data reveal a dopamine-to-glutamate signaling that regulates the bioavailability of ascorbate in neuronal cells. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019 2019-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://hdl.handle.net/10216/136216 |
url |
https://hdl.handle.net/10216/136216 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1662-4548 10.3389/fnins.2019.00453 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Media |
publisher.none.fl_str_mv |
Frontiers Media |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
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repository.mail.fl_str_mv |
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1777304193064763392 |