Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury

10 pages, 8 figures.-- PMID: 18671671 [PubMed].-- El pdf del artículo es la versión post-print.

Detalles Bibliográficos
Autores: Mayoral, Rafael, Mollá, Belén, Flores, Juana María, Boscá, Lisardo, Casado, Marta, Martín-Sanz, Paloma
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2008
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/13621
Acceso en línea:http://hdl.handle.net/10261/13621
Access Level:acceso abierto
Palabra clave:Prostaglandins
Lipopolysaccharide
Concanavalin A
Inflammation
Apoptosis
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spelling Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injuryMayoral, RafaelMollá, BelénFlores, Juana MaríaBoscá, LisardoCasado, MartaMartín-Sanz, PalomaProstaglandinsLipopolysaccharideConcanavalin AInflammationApoptosis10 pages, 8 figures.-- PMID: 18671671 [PubMed].-- El pdf del artículo es la versión post-print.The effect of COX-2-dependent prostaglandins (PGs) in acute liver injury has been investigated in transgenic mice that express human COX-2 in hepatocytes. We have used three well established models of liver injury: Lipopolysaccharide injury in D-galactosamine preconditioned mice (LPS/D-GalN), the hepatitis induced by concanavalin A (ConA) and the proliferation of hepatocytes in regenerating liver after partial hepatectomy (PH). Our data demonstrate that PGs synthesis decreases in hepatocytes the susceptibility to LPS/D-GalN or ConA-induced liver injury as deduced by significant lower levels of the pro-inflammatory profile and plasmatic aminotransferases in transgenic mice, an effect suppressed by COX-2 selective inhibitors. These transgenic animals express higher levels of anti-apoptotic proteins and exhibit activation of proteins implicated in cell survival, such as Akt and AMP-kinase after injury. The resistance to LPS/D-GalN induced liver apoptosis involves an impairment of procaspase 3 and 8 activation. Protection against ConA-induced injury implies a significant reduction in necrosis. Moreover, hepatocyte commitment to start replication is anticipated in Tg mice after PH, due to the expression of PCNA, cyclin D1 and E. These results show, in a genetic model, that tissue-specific COX-2 dependent PGs exert an efficient protection against acute liver injury by an antiapoptotic/antinecrotic effect and by accelerated early hepatocyte proliferation.This work was supported by grants SAF2007-60551, SAF2005-1758 and S-BIO-0283/2006. B. M. was supported by grant of FIS-RECAVA RD06/0014/0025. Ciberehd is funded by the Instituto de Salud Carlos III.Peer reviewedPortland PressBiochemical Society200920092008info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersion863943 bytesapplication/pdfhttp://hdl.handle.net/10261/13621reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1042/BJ20081224info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/136212026-05-22T06:33:51Z
dc.title.none.fl_str_mv Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury
title Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury
spellingShingle Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury
Mayoral, Rafael
Prostaglandins
Lipopolysaccharide
Concanavalin A
Inflammation
Apoptosis
title_short Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury
title_full Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury
title_fullStr Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury
title_full_unstemmed Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury
title_sort Constitutive expression of cyclo-oxygenase 2 transgene in hepatocytes protects against liver injury
dc.creator.none.fl_str_mv Mayoral, Rafael
Mollá, Belén
Flores, Juana María
Boscá, Lisardo
Casado, Marta
Martín-Sanz, Paloma
author Mayoral, Rafael
author_facet Mayoral, Rafael
Mollá, Belén
Flores, Juana María
Boscá, Lisardo
Casado, Marta
Martín-Sanz, Paloma
author_role author
author2 Mollá, Belén
Flores, Juana María
Boscá, Lisardo
Casado, Marta
Martín-Sanz, Paloma
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Prostaglandins
Lipopolysaccharide
Concanavalin A
Inflammation
Apoptosis
topic Prostaglandins
Lipopolysaccharide
Concanavalin A
Inflammation
Apoptosis
description 10 pages, 8 figures.-- PMID: 18671671 [PubMed].-- El pdf del artículo es la versión post-print.
publishDate 2008
dc.date.none.fl_str_mv 2008
2009
2009
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/13621
url http://hdl.handle.net/10261/13621
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1042/BJ20081224
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 863943 bytes
application/pdf
dc.publisher.none.fl_str_mv Portland Press
Biochemical Society
publisher.none.fl_str_mv Portland Press
Biochemical Society
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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