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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/4716
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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 |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
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dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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