Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levels
- Autores
- Echevarria, Maria Sol; Tenconi, Paula Estefania; Mateos, Melina Valeria
- Año de publicación
- 2022
- Idioma
- inglés
- Tipo de recurso
- documento de conferencia
- Estado
- versión publicada
- Descripción
- Objective: Oxidative stress (OE) and inflammation are involved in the pathogenesis of several retinal diseases. We previously demonstrated that classical phospholipase D isoforms (PLD1 and 2) mediate the inflammatory response of retinal pigment epithelium (RPE) cells induced by high glucose (HG) levels. Furthermore, a significant increase in reactive oxygen species (ROS) was observed in RPE cells exposed to HG. The aim of the present work was to study the relationship between OE and PLD activation observed in HG- treated RPE cells. Methods: RPE cells (ARPE-19) were exposed to HG (33 mM) or to normal glucose levels (NG, 5.5 mM) for 24 h. To inhibit PLD1, PLD2 and cyclooxygenase-2 (COX-2) VU0359595 (PLD1i, 0.5 μM), VU0285655-1 (PLD2i, 0.5 μM) or celecoxib (10 μM) were used, respectively. ROS production was assessed using the probe DCDCDHF. Immunocytochemistry assays (ICC) and western blots were performed to evaluate nuclear factor erythroid 2–related factor2 (Nrf-2) pathway. Results: HG-exposure for 24 h increased ROS levels (148%) in ARPE-19 cells with respect to NG. The incubation with PLD1i and PLD2i prevented HG-induced ROS generation in RPE cells. On the contrary, the inhibition of COX-2 was not able to prevent OE induced by HG. ICC showed Nrf-2 nuclear translocation in cells exposed to HG and this effect was not observed when cells were pre-treated with PLD1i and PLD2i. Nrf-2 activation correlated with and increased heme oxygenase-1 (HO-1) expression (42%) in HG-exposed cells but no differences were observed in cells treated with PLD1i or PLD2i with respect to NG. Conclusions: Our results demonstrate that PLD1 and PLD2 inhibition not only prevents the inflammatory response of RPE cells, but also decreases OE generated in RPE cells exposed to HG in a Nrf-2 and COX-2 independent manner. Further experiments are needed to fully elucidate the mechanisms by which the PLD pathway mediates OE in RPE cells exposed to inflammatory injury.
Fil: Echevarria, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Tenconi, Paula Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Mateos, Melina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Reunión Anual de Sociedades de Biociencias 2022: LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad argentina de inmunología; Reunión anual 2022 de la Sociedad Argentina de Fisiología
Mar de plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología - Materia
-
PHOSPHOLIPASE D
RETINAL PIGMENT EPITHELIUM
OXIDATIVE STRESS - 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:11336/228497
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Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levelsEchevarria, Maria SolTenconi, Paula EstefaniaMateos, Melina ValeriaPHOSPHOLIPASE DRETINAL PIGMENT EPITHELIUMOXIDATIVE STRESShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Objective: Oxidative stress (OE) and inflammation are involved in the pathogenesis of several retinal diseases. We previously demonstrated that classical phospholipase D isoforms (PLD1 and 2) mediate the inflammatory response of retinal pigment epithelium (RPE) cells induced by high glucose (HG) levels. Furthermore, a significant increase in reactive oxygen species (ROS) was observed in RPE cells exposed to HG. The aim of the present work was to study the relationship between OE and PLD activation observed in HG- treated RPE cells. Methods: RPE cells (ARPE-19) were exposed to HG (33 mM) or to normal glucose levels (NG, 5.5 mM) for 24 h. To inhibit PLD1, PLD2 and cyclooxygenase-2 (COX-2) VU0359595 (PLD1i, 0.5 μM), VU0285655-1 (PLD2i, 0.5 μM) or celecoxib (10 μM) were used, respectively. ROS production was assessed using the probe DCDCDHF. Immunocytochemistry assays (ICC) and western blots were performed to evaluate nuclear factor erythroid 2–related factor2 (Nrf-2) pathway. Results: HG-exposure for 24 h increased ROS levels (148%) in ARPE-19 cells with respect to NG. The incubation with PLD1i and PLD2i prevented HG-induced ROS generation in RPE cells. On the contrary, the inhibition of COX-2 was not able to prevent OE induced by HG. ICC showed Nrf-2 nuclear translocation in cells exposed to HG and this effect was not observed when cells were pre-treated with PLD1i and PLD2i. Nrf-2 activation correlated with and increased heme oxygenase-1 (HO-1) expression (42%) in HG-exposed cells but no differences were observed in cells treated with PLD1i or PLD2i with respect to NG. Conclusions: Our results demonstrate that PLD1 and PLD2 inhibition not only prevents the inflammatory response of RPE cells, but also decreases OE generated in RPE cells exposed to HG in a Nrf-2 and COX-2 independent manner. Further experiments are needed to fully elucidate the mechanisms by which the PLD pathway mediates OE in RPE cells exposed to inflammatory injury.Fil: Echevarria, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Tenconi, Paula Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Mateos, Melina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaReunión Anual de Sociedades de Biociencias 2022: LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad argentina de inmunología; Reunión anual 2022 de la Sociedad Argentina de FisiologíaMar de plataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina de FisiologíaFundación Revista MedicinaAlonso, Daniel FernandoMalchiodi, Emilio LuisVila Petroff, Martin GerardeLamb, Caroline Ana2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/228497Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levels; Reunión Anual de Sociedades de Biociencias 2022: LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad argentina de inmunología; Reunión anual 2022 de la Sociedad Argentina de Fisiología; Mar de plata; Argentina; 2022; 307-3070025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:21:08Zoai:ri.conicet.gov.ar:11336/228497instacron: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 10:21:09.211CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levels |
title |
Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levels |
spellingShingle |
Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levels Echevarria, Maria Sol PHOSPHOLIPASE D RETINAL PIGMENT EPITHELIUM OXIDATIVE STRESS |
title_short |
Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levels |
title_full |
Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levels |
title_fullStr |
Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levels |
title_full_unstemmed |
Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levels |
title_sort |
Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levels |
dc.creator.none.fl_str_mv |
Echevarria, Maria Sol Tenconi, Paula Estefania Mateos, Melina Valeria |
author |
Echevarria, Maria Sol |
author_facet |
Echevarria, Maria Sol Tenconi, Paula Estefania Mateos, Melina Valeria |
author_role |
author |
author2 |
Tenconi, Paula Estefania Mateos, Melina Valeria |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Alonso, Daniel Fernando Malchiodi, Emilio Luis Vila Petroff, Martin Gerarde Lamb, Caroline Ana |
dc.subject.none.fl_str_mv |
PHOSPHOLIPASE D RETINAL PIGMENT EPITHELIUM OXIDATIVE STRESS |
topic |
PHOSPHOLIPASE D RETINAL PIGMENT EPITHELIUM OXIDATIVE STRESS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Objective: Oxidative stress (OE) and inflammation are involved in the pathogenesis of several retinal diseases. We previously demonstrated that classical phospholipase D isoforms (PLD1 and 2) mediate the inflammatory response of retinal pigment epithelium (RPE) cells induced by high glucose (HG) levels. Furthermore, a significant increase in reactive oxygen species (ROS) was observed in RPE cells exposed to HG. The aim of the present work was to study the relationship between OE and PLD activation observed in HG- treated RPE cells. Methods: RPE cells (ARPE-19) were exposed to HG (33 mM) or to normal glucose levels (NG, 5.5 mM) for 24 h. To inhibit PLD1, PLD2 and cyclooxygenase-2 (COX-2) VU0359595 (PLD1i, 0.5 μM), VU0285655-1 (PLD2i, 0.5 μM) or celecoxib (10 μM) were used, respectively. ROS production was assessed using the probe DCDCDHF. Immunocytochemistry assays (ICC) and western blots were performed to evaluate nuclear factor erythroid 2–related factor2 (Nrf-2) pathway. Results: HG-exposure for 24 h increased ROS levels (148%) in ARPE-19 cells with respect to NG. The incubation with PLD1i and PLD2i prevented HG-induced ROS generation in RPE cells. On the contrary, the inhibition of COX-2 was not able to prevent OE induced by HG. ICC showed Nrf-2 nuclear translocation in cells exposed to HG and this effect was not observed when cells were pre-treated with PLD1i and PLD2i. Nrf-2 activation correlated with and increased heme oxygenase-1 (HO-1) expression (42%) in HG-exposed cells but no differences were observed in cells treated with PLD1i or PLD2i with respect to NG. Conclusions: Our results demonstrate that PLD1 and PLD2 inhibition not only prevents the inflammatory response of RPE cells, but also decreases OE generated in RPE cells exposed to HG in a Nrf-2 and COX-2 independent manner. Further experiments are needed to fully elucidate the mechanisms by which the PLD pathway mediates OE in RPE cells exposed to inflammatory injury. Fil: Echevarria, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Tenconi, Paula Estefania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Fil: Mateos, Melina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina Reunión Anual de Sociedades de Biociencias 2022: LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad argentina de inmunología; Reunión anual 2022 de la Sociedad Argentina de Fisiología Mar de plata Argentina Sociedad Argentina de Investigación Clínica Sociedad Argentina de Inmunología Sociedad Argentina de Fisiología |
description |
Objective: Oxidative stress (OE) and inflammation are involved in the pathogenesis of several retinal diseases. We previously demonstrated that classical phospholipase D isoforms (PLD1 and 2) mediate the inflammatory response of retinal pigment epithelium (RPE) cells induced by high glucose (HG) levels. Furthermore, a significant increase in reactive oxygen species (ROS) was observed in RPE cells exposed to HG. The aim of the present work was to study the relationship between OE and PLD activation observed in HG- treated RPE cells. Methods: RPE cells (ARPE-19) were exposed to HG (33 mM) or to normal glucose levels (NG, 5.5 mM) for 24 h. To inhibit PLD1, PLD2 and cyclooxygenase-2 (COX-2) VU0359595 (PLD1i, 0.5 μM), VU0285655-1 (PLD2i, 0.5 μM) or celecoxib (10 μM) were used, respectively. ROS production was assessed using the probe DCDCDHF. Immunocytochemistry assays (ICC) and western blots were performed to evaluate nuclear factor erythroid 2–related factor2 (Nrf-2) pathway. Results: HG-exposure for 24 h increased ROS levels (148%) in ARPE-19 cells with respect to NG. The incubation with PLD1i and PLD2i prevented HG-induced ROS generation in RPE cells. On the contrary, the inhibition of COX-2 was not able to prevent OE induced by HG. ICC showed Nrf-2 nuclear translocation in cells exposed to HG and this effect was not observed when cells were pre-treated with PLD1i and PLD2i. Nrf-2 activation correlated with and increased heme oxygenase-1 (HO-1) expression (42%) in HG-exposed cells but no differences were observed in cells treated with PLD1i or PLD2i with respect to NG. Conclusions: Our results demonstrate that PLD1 and PLD2 inhibition not only prevents the inflammatory response of RPE cells, but also decreases OE generated in RPE cells exposed to HG in a Nrf-2 and COX-2 independent manner. Further experiments are needed to fully elucidate the mechanisms by which the PLD pathway mediates OE in RPE cells exposed to inflammatory injury. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022 |
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info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/conferenceObject Congreso Journal http://purl.org/coar/resource_type/c_5794 info:ar-repo/semantics/documentoDeConferencia |
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http://hdl.handle.net/11336/228497 Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levels; Reunión Anual de Sociedades de Biociencias 2022: LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad argentina de inmunología; Reunión anual 2022 de la Sociedad Argentina de Fisiología; Mar de plata; Argentina; 2022; 307-307 0025-7680 1669-9106 CONICET Digital CONICET |
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http://hdl.handle.net/11336/228497 |
identifier_str_mv |
Phospholipase D 1 and 2 inhibition prevents oxidative stress in retinal pigment epithelium cells exposed to high glucose levels; Reunión Anual de Sociedades de Biociencias 2022: LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad argentina de inmunología; Reunión anual 2022 de la Sociedad Argentina de Fisiología; Mar de plata; Argentina; 2022; 307-307 0025-7680 1669-9106 CONICET Digital CONICET |
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eng |
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eng |
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Fundación Revista Medicina |
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