A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain

Autores
Omata, Yo; Salvador, Gabriela Alejandra; Supasai, Suangsuda; Keenan, Allison H.; Oteiza, Patricia Isabel
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Department of Nutrition and Department of Environmental Toxicology, University of California, Davis, California 95616. Abstract A deficit in zinc (Zn) availability can increase cell oxidant production, affect the antioxidant defense system, and trigger oxidant-sensitive signals in neuronal cells. This work tested the hypothesis that a decreased Zn availability can affect glutathione (GSH) metabolism in the developing rat brain and in neuronal cells in culture, as well as the capacity of human neuroblastoma IMR-32 cells to upregulate GSH when challenged with dopamine (DA). GSH levels were low in the brain of gestation day 19 (GD19) fetuses from dams fed marginal Zn diets throughout gestation and in Zn-deficient IMR-32 cells. γ-Glutamylcysteine synthetase (GCL), the first enzyme in the GSH synthetic pathway, was altered by Zn deficiency (ZD). The protein and mRNA levels of the GCL modifier (GCLM) and catalytic (GCLC) subunits were lower in the Zn-deficient GD19 fetal brain and in IMR-32 cells compared with controls. The nuclear translocation of transcription factor nuclear factor (erythroid-derived 2)-like 2, which controls GCL transcription, was impaired by ZD. Posttranslationally, the caspase-3-dependent GCLC cleavage was high in Zn-deficient IMR-32 cells. Cells challenged with DA showed an increase in GCLM and GCLC protein and mRNA levels and a consequent increase in GSH concentration. Although Zn-deficient cells partially upregulated GCL subunits after exposure to DA, GSH content remained low. In summary, results show that a low Zn availability affects the GSH synthetic pathway in neuronal cells and fetal brain both at transcriptional and posttranslational levels. This can in part underlie the GSH depletion associated with ZD and the high sensitivity of Zn-deficient neurons to pro-oxidative stressors.
Fil: Omata, Yo. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados Unidos
Fil: Salvador, Gabriela Alejandra. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Cientí­ficas y Técnicas. Centro Científico Tecnológico Bahí­a Blanca. Instituto de Investigaciones Bioquímicas Bahí­a Blanca (i); Argentina
Fil: Supasai, Suangsuda. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados Unidos
Fil: Keenan, Allison H.. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados Unidos
Fil: Oteiza, Patricia Isabel. University of California.Department of Nutrition and Department of Environmental Toxicology; Estados Unidos
Materia
ZINC
GLUTHATIONE
OXIDATIVE STRESS
BRAIN
DOPAMINE
NEURON
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/4716

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing BrainOmata, YoSalvador, Gabriela AlejandraSupasai, SuangsudaKeenan, Allison H.Oteiza, Patricia IsabelZINCGLUTHATIONEOXIDATIVE STRESSBRAINDOPAMINENEURONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Department of Nutrition and Department of Environmental Toxicology, University of California, Davis, California 95616. Abstract A deficit in zinc (Zn) availability can increase cell oxidant production, affect the antioxidant defense system, and trigger oxidant-sensitive signals in neuronal cells. This work tested the hypothesis that a decreased Zn availability can affect glutathione (GSH) metabolism in the developing rat brain and in neuronal cells in culture, as well as the capacity of human neuroblastoma IMR-32 cells to upregulate GSH when challenged with dopamine (DA). GSH levels were low in the brain of gestation day 19 (GD19) fetuses from dams fed marginal Zn diets throughout gestation and in Zn-deficient IMR-32 cells. γ-Glutamylcysteine synthetase (GCL), the first enzyme in the GSH synthetic pathway, was altered by Zn deficiency (ZD). The protein and mRNA levels of the GCL modifier (GCLM) and catalytic (GCLC) subunits were lower in the Zn-deficient GD19 fetal brain and in IMR-32 cells compared with controls. The nuclear translocation of transcription factor nuclear factor (erythroid-derived 2)-like 2, which controls GCL transcription, was impaired by ZD. Posttranslationally, the caspase-3-dependent GCLC cleavage was high in Zn-deficient IMR-32 cells. Cells challenged with DA showed an increase in GCLM and GCLC protein and mRNA levels and a consequent increase in GSH concentration. Although Zn-deficient cells partially upregulated GCL subunits after exposure to DA, GSH content remained low. In summary, results show that a low Zn availability affects the GSH synthetic pathway in neuronal cells and fetal brain both at transcriptional and posttranslational levels. This can in part underlie the GSH depletion associated with ZD and the high sensitivity of Zn-deficient neurons to pro-oxidative stressors.Fil: Omata, Yo. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados UnidosFil: Salvador, Gabriela Alejandra. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Cientí­ficas y Técnicas. Centro Científico Tecnológico Bahí­a Blanca. Instituto de Investigaciones Bioquímicas Bahí­a Blanca (i); ArgentinaFil: Supasai, Suangsuda. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados UnidosFil: Keenan, Allison H.. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados UnidosFil: Oteiza, Patricia Isabel. University of California.Department of Nutrition and Department of Environmental Toxicology; Estados UnidosOxford University Press2013-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/4716Omata, Yo; Salvador, Gabriela Alejandra; Supasai, Suangsuda; Keenan, Allison H.; Oteiza, Patricia Isabel; A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain; Oxford University Press; Toxicological Sciences; 133; 1; 1-2013; 90-1001096-6080enginfo:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627551/info:eu-repo/semantics/altIdentifier/url/http://toxsci.oxfordjournals.org/content/133/1/90.longinfo:eu-repo/semantics/altIdentifier/doi/10.1093/toxsci/kft022info:eu-repo/semantics/altIdentifier/issn/1096-6080info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:50:00Zoai:ri.conicet.gov.ar:11336/4716instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:50:00.784CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain
title A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain
spellingShingle A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain
Omata, Yo
ZINC
GLUTHATIONE
OXIDATIVE STRESS
BRAIN
DOPAMINE
NEURON
title_short A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain
title_full A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain
title_fullStr A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain
title_full_unstemmed A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain
title_sort A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain
dc.creator.none.fl_str_mv Omata, Yo
Salvador, Gabriela Alejandra
Supasai, Suangsuda
Keenan, Allison H.
Oteiza, Patricia Isabel
author Omata, Yo
author_facet Omata, Yo
Salvador, Gabriela Alejandra
Supasai, Suangsuda
Keenan, Allison H.
Oteiza, Patricia Isabel
author_role author
author2 Salvador, Gabriela Alejandra
Supasai, Suangsuda
Keenan, Allison H.
Oteiza, Patricia Isabel
author2_role author
author
author
author
dc.subject.none.fl_str_mv ZINC
GLUTHATIONE
OXIDATIVE STRESS
BRAIN
DOPAMINE
NEURON
topic ZINC
GLUTHATIONE
OXIDATIVE STRESS
BRAIN
DOPAMINE
NEURON
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Department of Nutrition and Department of Environmental Toxicology, University of California, Davis, California 95616. Abstract A deficit in zinc (Zn) availability can increase cell oxidant production, affect the antioxidant defense system, and trigger oxidant-sensitive signals in neuronal cells. This work tested the hypothesis that a decreased Zn availability can affect glutathione (GSH) metabolism in the developing rat brain and in neuronal cells in culture, as well as the capacity of human neuroblastoma IMR-32 cells to upregulate GSH when challenged with dopamine (DA). GSH levels were low in the brain of gestation day 19 (GD19) fetuses from dams fed marginal Zn diets throughout gestation and in Zn-deficient IMR-32 cells. γ-Glutamylcysteine synthetase (GCL), the first enzyme in the GSH synthetic pathway, was altered by Zn deficiency (ZD). The protein and mRNA levels of the GCL modifier (GCLM) and catalytic (GCLC) subunits were lower in the Zn-deficient GD19 fetal brain and in IMR-32 cells compared with controls. The nuclear translocation of transcription factor nuclear factor (erythroid-derived 2)-like 2, which controls GCL transcription, was impaired by ZD. Posttranslationally, the caspase-3-dependent GCLC cleavage was high in Zn-deficient IMR-32 cells. Cells challenged with DA showed an increase in GCLM and GCLC protein and mRNA levels and a consequent increase in GSH concentration. Although Zn-deficient cells partially upregulated GCL subunits after exposure to DA, GSH content remained low. In summary, results show that a low Zn availability affects the GSH synthetic pathway in neuronal cells and fetal brain both at transcriptional and posttranslational levels. This can in part underlie the GSH depletion associated with ZD and the high sensitivity of Zn-deficient neurons to pro-oxidative stressors.
Fil: Omata, Yo. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados Unidos
Fil: Salvador, Gabriela Alejandra. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Cientí­ficas y Técnicas. Centro Científico Tecnológico Bahí­a Blanca. Instituto de Investigaciones Bioquímicas Bahí­a Blanca (i); Argentina
Fil: Supasai, Suangsuda. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados Unidos
Fil: Keenan, Allison H.. University of California. Department of Nutrition and Department of Environmental Toxicology; Estados Unidos
Fil: Oteiza, Patricia Isabel. University of California.Department of Nutrition and Department of Environmental Toxicology; Estados Unidos
description Department of Nutrition and Department of Environmental Toxicology, University of California, Davis, California 95616. Abstract A deficit in zinc (Zn) availability can increase cell oxidant production, affect the antioxidant defense system, and trigger oxidant-sensitive signals in neuronal cells. This work tested the hypothesis that a decreased Zn availability can affect glutathione (GSH) metabolism in the developing rat brain and in neuronal cells in culture, as well as the capacity of human neuroblastoma IMR-32 cells to upregulate GSH when challenged with dopamine (DA). GSH levels were low in the brain of gestation day 19 (GD19) fetuses from dams fed marginal Zn diets throughout gestation and in Zn-deficient IMR-32 cells. γ-Glutamylcysteine synthetase (GCL), the first enzyme in the GSH synthetic pathway, was altered by Zn deficiency (ZD). The protein and mRNA levels of the GCL modifier (GCLM) and catalytic (GCLC) subunits were lower in the Zn-deficient GD19 fetal brain and in IMR-32 cells compared with controls. The nuclear translocation of transcription factor nuclear factor (erythroid-derived 2)-like 2, which controls GCL transcription, was impaired by ZD. Posttranslationally, the caspase-3-dependent GCLC cleavage was high in Zn-deficient IMR-32 cells. Cells challenged with DA showed an increase in GCLM and GCLC protein and mRNA levels and a consequent increase in GSH concentration. Although Zn-deficient cells partially upregulated GCL subunits after exposure to DA, GSH content remained low. In summary, results show that a low Zn availability affects the GSH synthetic pathway in neuronal cells and fetal brain both at transcriptional and posttranslational levels. This can in part underlie the GSH depletion associated with ZD and the high sensitivity of Zn-deficient neurons to pro-oxidative stressors.
publishDate 2013
dc.date.none.fl_str_mv 2013-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/4716
Omata, Yo; Salvador, Gabriela Alejandra; Supasai, Suangsuda; Keenan, Allison H.; Oteiza, Patricia Isabel; A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain; Oxford University Press; Toxicological Sciences; 133; 1; 1-2013; 90-100
1096-6080
url http://hdl.handle.net/11336/4716
identifier_str_mv Omata, Yo; Salvador, Gabriela Alejandra; Supasai, Suangsuda; Keenan, Allison H.; Oteiza, Patricia Isabel; A Decreased Zinc Availability Affects Glutathione Metabolism in Neuronal Cells and in the Developing Brain; Oxford University Press; Toxicological Sciences; 133; 1; 1-2013; 90-100
1096-6080
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3627551/
info:eu-repo/semantics/altIdentifier/url/http://toxsci.oxfordjournals.org/content/133/1/90.long
info:eu-repo/semantics/altIdentifier/doi/10.1093/toxsci/kft022
info:eu-repo/semantics/altIdentifier/issn/1096-6080
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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