Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degeneration

Autores
Rodriguez Diez, Guadalupe; Sánchez Campos, Sofía; Giusto, Norma Maria; Salvador, Gabriela Alejandra
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Iron accumulation and oxidative stress are hallmarks of retinas from patients with age-related macular degeneration (AMD). We have previously demonstrated that iron-overloaded retinas are a good in vitro model for the study of retinal degeneration during iron-induced oxidative stress. In this model we have previously characterized the role of cytosolic phospholipase A2 (cPLA2) and calcium-independent isoform (iPLA2). The aim of the present study was to analyze the implications of Group V secretory PLA2 (sPLA2), another member of PLA2 family, in cyclooxygenase (COX)-2 and nuclear factor kappa B (NF-κB) regulation. We found that sPLA2 is localized in cytosolic fraction in an iron concentration-dependent manner. By immunoprecipitation (IP) assays we also demonstrated an increased association between Group V sPLA2 and COX-2 in retinas exposed to iron overload. However, COX-2 activity in IP assays was observed to decrease in spite of the increased protein levels observed. p65 (RelA) NF-κB levels were increased in nuclear fractions from retinas exposed to iron. In the presence of ATK (cPLA2 inhibitor) and YM 26734 (sPLA2 inhibitor), the nuclear localization of both p65 and p50 NF-κB subunits was restored to control levels in retinas exposed to iron-induced oxidative stress. Membrane repair mechanisms were also analyzed by studying the participation of acyltransferases in phospholipid remodeling during retinal oxidation stress. Acidic phospholipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS), were observed to show an inhibited acylation profile in retinas exposed to iron while phosphatidylethanolamine (PE) showed the opposite. The use of PLA2 inhibitors demonstrated that PS is actively deacylated during iron-induced oxidative stress. Results from the present study suggest that Group V sPLA2 has multiple intracellular targets during iron-induced retinal degeneration and that the specific role of sPLA2 could be related to inflammatory responses by its participation in NF-κB and COX-2 regulation.
Fil: Rodriguez Diez, Guadalupe. 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: Sánchez Campos, Sofía. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Giusto, Norma Maria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Materia
Retina
Iron
Phospholipase A2
Macular Degeneration
Oxidative Stress
Acyltransferases
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/4820
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/4820
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degenerationRodriguez Diez, GuadalupeSánchez Campos, SofíaGiusto, Norma MariaSalvador, Gabriela AlejandraRetinaIronPhospholipase A2Macular DegenerationOxidative StressAcyltransferaseshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Iron accumulation and oxidative stress are hallmarks of retinas from patients with age-related macular degeneration (AMD). We have previously demonstrated that iron-overloaded retinas are a good in vitro model for the study of retinal degeneration during iron-induced oxidative stress. In this model we have previously characterized the role of cytosolic phospholipase A2 (cPLA2) and calcium-independent isoform (iPLA2). The aim of the present study was to analyze the implications of Group V secretory PLA2 (sPLA2), another member of PLA2 family, in cyclooxygenase (COX)-2 and nuclear factor kappa B (NF-κB) regulation. We found that sPLA2 is localized in cytosolic fraction in an iron concentration-dependent manner. By immunoprecipitation (IP) assays we also demonstrated an increased association between Group V sPLA2 and COX-2 in retinas exposed to iron overload. However, COX-2 activity in IP assays was observed to decrease in spite of the increased protein levels observed. p65 (RelA) NF-κB levels were increased in nuclear fractions from retinas exposed to iron. In the presence of ATK (cPLA2 inhibitor) and YM 26734 (sPLA2 inhibitor), the nuclear localization of both p65 and p50 NF-κB subunits was restored to control levels in retinas exposed to iron-induced oxidative stress. Membrane repair mechanisms were also analyzed by studying the participation of acyltransferases in phospholipid remodeling during retinal oxidation stress. Acidic phospholipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS), were observed to show an inhibited acylation profile in retinas exposed to iron while phosphatidylethanolamine (PE) showed the opposite. The use of PLA2 inhibitors demonstrated that PS is actively deacylated during iron-induced oxidative stress. Results from the present study suggest that Group V sPLA2 has multiple intracellular targets during iron-induced retinal degeneration and that the specific role of sPLA2 could be related to inflammatory responses by its participation in NF-κB and COX-2 regulation.Fil: Rodriguez Diez, Guadalupe. 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: Sánchez Campos, Sofía. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Giusto, Norma Maria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaElsevier2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/vnd.openxmlformats-officedocument.wordprocessingml.documentapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/4820Rodriguez Diez, Guadalupe; Sánchez Campos, Sofía; Giusto, Norma Maria; Salvador, Gabriela Alejandra; Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degeneration; Elsevier; Experimental Eye Research; 113; 6-2013; 172-1810014-4835enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014483513001383info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pubmed/23791636info:eu-repo/semantics/altIdentifier/pmid/23791636info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exer.2013.05.019info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:26:03Zoai:ri.conicet.gov.ar:11336/4820instacron: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 10:26:04.21CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degeneration
title Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degeneration
spellingShingle Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degeneration
Rodriguez Diez, Guadalupe
Retina
Iron
Phospholipase A2
Macular Degeneration
Oxidative Stress
Acyltransferases
title_short Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degeneration
title_full Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degeneration
title_fullStr Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degeneration
title_full_unstemmed Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degeneration
title_sort Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degeneration
dc.creator.none.fl_str_mv Rodriguez Diez, Guadalupe
Sánchez Campos, Sofía
Giusto, Norma Maria
Salvador, Gabriela Alejandra
author Rodriguez Diez, Guadalupe
author_facet Rodriguez Diez, Guadalupe
Sánchez Campos, Sofía
Giusto, Norma Maria
Salvador, Gabriela Alejandra
author_role author
author2 Sánchez Campos, Sofía
Giusto, Norma Maria
Salvador, Gabriela Alejandra
author2_role author
author
author
dc.subject.none.fl_str_mv Retina
Iron
Phospholipase A2
Macular Degeneration
Oxidative Stress
Acyltransferases
topic Retina
Iron
Phospholipase A2
Macular Degeneration
Oxidative Stress
Acyltransferases
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Iron accumulation and oxidative stress are hallmarks of retinas from patients with age-related macular degeneration (AMD). We have previously demonstrated that iron-overloaded retinas are a good in vitro model for the study of retinal degeneration during iron-induced oxidative stress. In this model we have previously characterized the role of cytosolic phospholipase A2 (cPLA2) and calcium-independent isoform (iPLA2). The aim of the present study was to analyze the implications of Group V secretory PLA2 (sPLA2), another member of PLA2 family, in cyclooxygenase (COX)-2 and nuclear factor kappa B (NF-κB) regulation. We found that sPLA2 is localized in cytosolic fraction in an iron concentration-dependent manner. By immunoprecipitation (IP) assays we also demonstrated an increased association between Group V sPLA2 and COX-2 in retinas exposed to iron overload. However, COX-2 activity in IP assays was observed to decrease in spite of the increased protein levels observed. p65 (RelA) NF-κB levels were increased in nuclear fractions from retinas exposed to iron. In the presence of ATK (cPLA2 inhibitor) and YM 26734 (sPLA2 inhibitor), the nuclear localization of both p65 and p50 NF-κB subunits was restored to control levels in retinas exposed to iron-induced oxidative stress. Membrane repair mechanisms were also analyzed by studying the participation of acyltransferases in phospholipid remodeling during retinal oxidation stress. Acidic phospholipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS), were observed to show an inhibited acylation profile in retinas exposed to iron while phosphatidylethanolamine (PE) showed the opposite. The use of PLA2 inhibitors demonstrated that PS is actively deacylated during iron-induced oxidative stress. Results from the present study suggest that Group V sPLA2 has multiple intracellular targets during iron-induced retinal degeneration and that the specific role of sPLA2 could be related to inflammatory responses by its participation in NF-κB and COX-2 regulation.
Fil: Rodriguez Diez, Guadalupe. 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: Sánchez Campos, Sofía. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Giusto, Norma Maria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnol.conicet - Bahia Blanca. Instituto de Invest.bioquimicas Bahia Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Salvador, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
description Iron accumulation and oxidative stress are hallmarks of retinas from patients with age-related macular degeneration (AMD). We have previously demonstrated that iron-overloaded retinas are a good in vitro model for the study of retinal degeneration during iron-induced oxidative stress. In this model we have previously characterized the role of cytosolic phospholipase A2 (cPLA2) and calcium-independent isoform (iPLA2). The aim of the present study was to analyze the implications of Group V secretory PLA2 (sPLA2), another member of PLA2 family, in cyclooxygenase (COX)-2 and nuclear factor kappa B (NF-κB) regulation. We found that sPLA2 is localized in cytosolic fraction in an iron concentration-dependent manner. By immunoprecipitation (IP) assays we also demonstrated an increased association between Group V sPLA2 and COX-2 in retinas exposed to iron overload. However, COX-2 activity in IP assays was observed to decrease in spite of the increased protein levels observed. p65 (RelA) NF-κB levels were increased in nuclear fractions from retinas exposed to iron. In the presence of ATK (cPLA2 inhibitor) and YM 26734 (sPLA2 inhibitor), the nuclear localization of both p65 and p50 NF-κB subunits was restored to control levels in retinas exposed to iron-induced oxidative stress. Membrane repair mechanisms were also analyzed by studying the participation of acyltransferases in phospholipid remodeling during retinal oxidation stress. Acidic phospholipids, such as phosphatidylinositol (PI) and phosphatidylserine (PS), were observed to show an inhibited acylation profile in retinas exposed to iron while phosphatidylethanolamine (PE) showed the opposite. The use of PLA2 inhibitors demonstrated that PS is actively deacylated during iron-induced oxidative stress. Results from the present study suggest that Group V sPLA2 has multiple intracellular targets during iron-induced retinal degeneration and that the specific role of sPLA2 could be related to inflammatory responses by its participation in NF-κB and COX-2 regulation.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
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/11336/4820
Rodriguez Diez, Guadalupe; Sánchez Campos, Sofía; Giusto, Norma Maria; Salvador, Gabriela Alejandra; Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degeneration; Elsevier; Experimental Eye Research; 113; 6-2013; 172-181
0014-4835
url http://hdl.handle.net/11336/4820
identifier_str_mv Rodriguez Diez, Guadalupe; Sánchez Campos, Sofía; Giusto, Norma Maria; Salvador, Gabriela Alejandra; Specific roles for Group V secretory PLA2 in retinal iron-induced oxidative stress. Implications for age-related macular degeneration; Elsevier; Experimental Eye Research; 113; 6-2013; 172-181
0014-4835
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014483513001383
info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pubmed/23791636
info:eu-repo/semantics/altIdentifier/pmid/23791636
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exer.2013.05.019
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/vnd.openxmlformats-officedocument.wordprocessingml.document
application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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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