Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia

Autores
Frances, Daniel Eleazar Antonio; Ingaramo, Paola Inés; Mayoral, Rafael; Través, Paqui; Casado, Marta; Valverde, Angela M.; Martin Sanz, Paloma; Carnovale, Cristina Ester
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Increased expression of COX-2 has been linked to inflammation and carcinogenesis. Constitutive expression of COX-2 protects hepatocytes from several pro-apoptotic stimuli. Increased hepatic apoptosis has been observed in experimental models of diabetes. Our present aim was to analyze the role of COX-2 as a regulator of apoptosis in diabetic mouse liver. Mice of C57BL/6 strain Wild Type (Wt) and transgenic in COX-2 (hCOX-2 Tg) were separated into Control (vehicle) and SID (Streptozotocin Induced Diabetes, 200mg/kg body weight, i.p.). Seven days post-injection, Wt diabetic animals showed a decrease in PI3K activity and P-Akt levels, an increase of P-JNK, P-p38, pro-apoptotic Bad and Bax, release of cytochrome c and activities of caspases-3 and -9, leading to an increased apoptotic index. This situation was improved in diabetic COX-2 Tg. In addition, SID COX-2 Tg showed increased expression of anti-apoptotic Mcl-1 and XIAP. Pro-apoptotic state in the liver of diabetic animals was improved by over-expression of COX-2. We also analyzed the roles of high glucose-induced apoptosis and hCOX-2 in vitro. Non-transfected and hCOX-2-transfected cells were cultured at 5 mM and 25 mM of glucose by 72 hours. At 25 mM there was an increase in apoptosis in non-transfected cells vs those exposed to 5 mM. This increase was partly prevented in transfected cells at 25 mM. Moreover, the protective effect observed in hCOX-2-transfected cells was suppressed by addition of DFU (COX-2 selective inhibitor), and mimicked by addition of PGE2 in non-tranfected cells. Taken together, these results demonstrate that hyperglycemia-induced hepatic apoptosis is protected by hCOX-2 expression.
Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Ingaramo, Paola Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Mayoral, Rafael. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España
Fil: Través, Paqui. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España
Fil: Casado, Marta. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España. Consejo Superior de Investigaciones Científicas. Instituto de Biomedicina de Valencia; España
Fil: Valverde, Angela M.. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España
Fil: Martin Sanz, Paloma. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. Centro de Investigacón Biomédica en Red de Enfermedades Hepáticas y Digestivas; España
Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Materia
Cox-2
Liver
Apoptosis
Diabetes
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:11336/6125
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/6125
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemiaFrances, Daniel Eleazar AntonioIngaramo, Paola InésMayoral, RafaelTravés, PaquiCasado, MartaValverde, Angela M.Martin Sanz, PalomaCarnovale, Cristina EsterCox-2LiverApoptosisDiabeteshttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Increased expression of COX-2 has been linked to inflammation and carcinogenesis. Constitutive expression of COX-2 protects hepatocytes from several pro-apoptotic stimuli. Increased hepatic apoptosis has been observed in experimental models of diabetes. Our present aim was to analyze the role of COX-2 as a regulator of apoptosis in diabetic mouse liver. Mice of C57BL/6 strain Wild Type (Wt) and transgenic in COX-2 (hCOX-2 Tg) were separated into Control (vehicle) and SID (Streptozotocin Induced Diabetes, 200mg/kg body weight, i.p.). Seven days post-injection, Wt diabetic animals showed a decrease in PI3K activity and P-Akt levels, an increase of P-JNK, P-p38, pro-apoptotic Bad and Bax, release of cytochrome c and activities of caspases-3 and -9, leading to an increased apoptotic index. This situation was improved in diabetic COX-2 Tg. In addition, SID COX-2 Tg showed increased expression of anti-apoptotic Mcl-1 and XIAP. Pro-apoptotic state in the liver of diabetic animals was improved by over-expression of COX-2. We also analyzed the roles of high glucose-induced apoptosis and hCOX-2 in vitro. Non-transfected and hCOX-2-transfected cells were cultured at 5 mM and 25 mM of glucose by 72 hours. At 25 mM there was an increase in apoptosis in non-transfected cells vs those exposed to 5 mM. This increase was partly prevented in transfected cells at 25 mM. Moreover, the protective effect observed in hCOX-2-transfected cells was suppressed by addition of DFU (COX-2 selective inhibitor), and mimicked by addition of PGE2 in non-tranfected cells. Taken together, these results demonstrate that hyperglycemia-induced hepatic apoptosis is protected by hCOX-2 expression.Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Ingaramo, Paola Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Mayoral, Rafael. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; EspañaFil: Través, Paqui. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; EspañaFil: Casado, Marta. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España. Consejo Superior de Investigaciones Científicas. Instituto de Biomedicina de Valencia; EspañaFil: Valverde, Angela M.. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; EspañaFil: Martin Sanz, Paloma. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. Centro de Investigacón Biomédica en Red de Enfermedades Hepáticas y Digestivas; EspañaFil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaWiley2013-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6125Frances, Daniel Eleazar Antonio; Ingaramo, Paola Inés; Mayoral, Rafael; Través, Paqui; Casado, Marta; et al.; Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia; Wiley; Journal of Cellular Biochemistry; 114; 3; 3-2013; 669-6800730-2312enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/wol1/doi/10.1002/jcb.24409/abstractinfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/doi/10.1002/jcb.24409info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:41:35Zoai:ri.conicet.gov.ar:11336/6125instacron: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 10:41:35.483CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia
title Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia
spellingShingle Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia
Frances, Daniel Eleazar Antonio
Cox-2
Liver
Apoptosis
Diabetes
title_short Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia
title_full Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia
title_fullStr Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia
title_full_unstemmed Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia
title_sort Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia
dc.creator.none.fl_str_mv Frances, Daniel Eleazar Antonio
Ingaramo, Paola Inés
Mayoral, Rafael
Través, Paqui
Casado, Marta
Valverde, Angela M.
Martin Sanz, Paloma
Carnovale, Cristina Ester
author Frances, Daniel Eleazar Antonio
author_facet Frances, Daniel Eleazar Antonio
Ingaramo, Paola Inés
Mayoral, Rafael
Través, Paqui
Casado, Marta
Valverde, Angela M.
Martin Sanz, Paloma
Carnovale, Cristina Ester
author_role author
author2 Ingaramo, Paola Inés
Mayoral, Rafael
Través, Paqui
Casado, Marta
Valverde, Angela M.
Martin Sanz, Paloma
Carnovale, Cristina Ester
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cox-2
Liver
Apoptosis
Diabetes
topic Cox-2
Liver
Apoptosis
Diabetes
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Increased expression of COX-2 has been linked to inflammation and carcinogenesis. Constitutive expression of COX-2 protects hepatocytes from several pro-apoptotic stimuli. Increased hepatic apoptosis has been observed in experimental models of diabetes. Our present aim was to analyze the role of COX-2 as a regulator of apoptosis in diabetic mouse liver. Mice of C57BL/6 strain Wild Type (Wt) and transgenic in COX-2 (hCOX-2 Tg) were separated into Control (vehicle) and SID (Streptozotocin Induced Diabetes, 200mg/kg body weight, i.p.). Seven days post-injection, Wt diabetic animals showed a decrease in PI3K activity and P-Akt levels, an increase of P-JNK, P-p38, pro-apoptotic Bad and Bax, release of cytochrome c and activities of caspases-3 and -9, leading to an increased apoptotic index. This situation was improved in diabetic COX-2 Tg. In addition, SID COX-2 Tg showed increased expression of anti-apoptotic Mcl-1 and XIAP. Pro-apoptotic state in the liver of diabetic animals was improved by over-expression of COX-2. We also analyzed the roles of high glucose-induced apoptosis and hCOX-2 in vitro. Non-transfected and hCOX-2-transfected cells were cultured at 5 mM and 25 mM of glucose by 72 hours. At 25 mM there was an increase in apoptosis in non-transfected cells vs those exposed to 5 mM. This increase was partly prevented in transfected cells at 25 mM. Moreover, the protective effect observed in hCOX-2-transfected cells was suppressed by addition of DFU (COX-2 selective inhibitor), and mimicked by addition of PGE2 in non-tranfected cells. Taken together, these results demonstrate that hyperglycemia-induced hepatic apoptosis is protected by hCOX-2 expression.
Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Ingaramo, Paola Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Mayoral, Rafael. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España
Fil: Través, Paqui. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España
Fil: Casado, Marta. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas; España. Consejo Superior de Investigaciones Científicas. Instituto de Biomedicina de Valencia; España
Fil: Valverde, Angela M.. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas; España
Fil: Martin Sanz, Paloma. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. Centro de Investigacón Biomédica en Red de Enfermedades Hepáticas y Digestivas; España
Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
description Increased expression of COX-2 has been linked to inflammation and carcinogenesis. Constitutive expression of COX-2 protects hepatocytes from several pro-apoptotic stimuli. Increased hepatic apoptosis has been observed in experimental models of diabetes. Our present aim was to analyze the role of COX-2 as a regulator of apoptosis in diabetic mouse liver. Mice of C57BL/6 strain Wild Type (Wt) and transgenic in COX-2 (hCOX-2 Tg) were separated into Control (vehicle) and SID (Streptozotocin Induced Diabetes, 200mg/kg body weight, i.p.). Seven days post-injection, Wt diabetic animals showed a decrease in PI3K activity and P-Akt levels, an increase of P-JNK, P-p38, pro-apoptotic Bad and Bax, release of cytochrome c and activities of caspases-3 and -9, leading to an increased apoptotic index. This situation was improved in diabetic COX-2 Tg. In addition, SID COX-2 Tg showed increased expression of anti-apoptotic Mcl-1 and XIAP. Pro-apoptotic state in the liver of diabetic animals was improved by over-expression of COX-2. We also analyzed the roles of high glucose-induced apoptosis and hCOX-2 in vitro. Non-transfected and hCOX-2-transfected cells were cultured at 5 mM and 25 mM of glucose by 72 hours. At 25 mM there was an increase in apoptosis in non-transfected cells vs those exposed to 5 mM. This increase was partly prevented in transfected cells at 25 mM. Moreover, the protective effect observed in hCOX-2-transfected cells was suppressed by addition of DFU (COX-2 selective inhibitor), and mimicked by addition of PGE2 in non-tranfected cells. Taken together, these results demonstrate that hyperglycemia-induced hepatic apoptosis is protected by hCOX-2 expression.
publishDate 2013
dc.date.none.fl_str_mv 2013-03
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/11336/6125
Frances, Daniel Eleazar Antonio; Ingaramo, Paola Inés; Mayoral, Rafael; Través, Paqui; Casado, Marta; et al.; Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia; Wiley; Journal of Cellular Biochemistry; 114; 3; 3-2013; 669-680
0730-2312
url http://hdl.handle.net/11336/6125
identifier_str_mv Frances, Daniel Eleazar Antonio; Ingaramo, Paola Inés; Mayoral, Rafael; Través, Paqui; Casado, Marta; et al.; Cyclooxygenase-2 over-expression inhibits liver apoptosis induced by hyperglycemia; Wiley; Journal of Cellular Biochemistry; 114; 3; 3-2013; 669-680
0730-2312
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/wol1/doi/10.1002/jcb.24409/abstract
info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/doi/10.1002/jcb.24409
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
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
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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score 13.070432

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