dc.contributor.author | Espinosa-Díez, Cristina | |
dc.contributor.author | Miguel, Verónica | |
dc.contributor.author | Vallejo, Susana | |
dc.contributor.author | Sánchez, Francisco J. | |
dc.contributor.author | Sandoval, Elena | |
dc.contributor.author | Blanco, Eva | |
dc.contributor.author | Cannata, Pablo | |
dc.contributor.author | Peiró Vallejo, M. Concepción | |
dc.contributor.author | Sánchez Ferrer, Carlos Félix | |
dc.contributor.author | Lamas, Santiago | |
dc.contributor.other | UAM. Departamento de Anatomía Patológica | es_ES |
dc.contributor.other | UAM. Departamento de Farmacología | es_ES |
dc.contributor.other | Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD) | es_ES |
dc.contributor.other | Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ) | es_ES |
dc.contributor.other | Centro de Biología Molecular Severo Ochoa (CBM) | es_ES |
dc.date.accessioned | 2018-03-21T18:08:06Z | |
dc.date.available | 2018-03-21T18:08:06Z | |
dc.date.issued | 2018-04-01 | |
dc.identifier.citation | Redox Biology 14 (2018): 88-99 | en_US |
dc.identifier.issn | 2213-2317 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10486/681583 | |
dc.description.abstract | Glutathione (GSH) biosynthesis is essential for cellular redox homeostasis and antioxidant defense. The rate-limiting step requires glutamate-cysteine ligase (GCL), which is composed of the catalytic (GCLc) and the modulatory (GCLm) subunits. To evaluate the contribution of GCLc to endothelial function we generated an endothelial-specific Gclc haplo-insufficient mouse model (Gclc e/+ mice). In murine lung endothelial cells (MLEC) derived from these mice we observed a 50% reduction in GCLc levels compared to lung fibroblasts from the same mice. MLEC obtained from haplo-insufficient mice showed significant reduction in GSH levels as well as increased basal and stimulated ROS levels, reduced phosphorylation of eNOS (Ser 1177) and increased eNOS S-glutathionylation, compared to MLEC from wild type (WT) mice. Studies in mesenteric arteries demonstrated impaired endothelium-dependent vasodilation in Gclc(e/+) male mice, which was corrected by pre-incubation with GSH-ethyl-ester and BH 4 . To study the contribution of endothelial GSH synthesis to renal fibrosis we employed the unilateral ureteral obstruction model in WT and Gclc(e/+) mice. We observed that obstructed kidneys from Gclc(e/+) mice exhibited increased deposition of fibrotic markers and reduced Nrf2 levels. We conclude that the preservation of endothelial GSH biosynthesis is not only critical for endothelial function but also in anti-fibrotic responses | en_US |
dc.description.sponsorship | This work was supported by grants from the Ministerio de Economía
y Competitividad (MINECO) SAF2012-31338, SAF2014-52762-R,
SAF2015-66107-R also supported by European Regional Development
Funds (ERDF-FEDER), and CSD 2007-00020, Instituto de Salud Carlos
III REDinREN RD12/0021/0009, RD16/0009/0016, Comunidad de
Madrid “Fibroteam” S2010/BMD-2321, and Fundación Renal “Iñigo
Alvarez de Toledo,” all from Spain. This study was supported by the
European Cooperation in Science and Research COST actions BM-1203
(EU-ROS) and BM-1005 (ENOGAS). The CBMSO receives institutional
support from Fundación “Ramón Areces”. Verónica Miguel is currently
supported by the MINECO program of Formación de Personal
Investigador (FPI BES-2013-065986). Cristina Espinosa-Diez was a
fellow of the FPI program from MINECO (BES-2010-035389) | en_US |
dc.format.extent | 12 pag. | es_ES |
dc.format.mimetype | application/pdf | en |
dc.language.iso | eng | en |
dc.publisher | Elsevier B.V. | en |
dc.relation.ispartof | Redox Biology | en_US |
dc.rights | © 2017 The Authors | en_US |
dc.subject.other | Endothelial dysfunction | en_US |
dc.subject.other | Glutamate-cysteine ligase | en_US |
dc.subject.other | Glutathione | en_US |
dc.subject.other | Kidney Fibrosis | en_US |
dc.subject.other | ROS | en_US |
dc.title | Role of glutathione biosynthesis in endothelial dysfunction and fibrosis | en_US |
dc.type | article | en |
dc.subject.eciencia | Biología y Biomedicina / Biología | es_ES |
dc.subject.eciencia | Farmacia | es_ES |
dc.relation.publisherversion | http://dx.doi.org/10.1016/j.redox.2017.08.019 | es_ES |
dc.identifier.doi | 10.1016/j.redox.2017.08.019 | es_ES |
dc.identifier.publicationfirstpage | 88 | es_ES |
dc.identifier.publicationissue | 14 | es_ES |
dc.identifier.publicationlastpage | 99 | es_ES |
dc.relation.projectID | Gobierno de España. SAF2012-31338 | es_ES |
dc.relation.projectID | Gobierno de España. SAF2014-52762-R | es_ES |
dc.relation.projectID | Gobierno de España. SAF2015-66107-R | es_ES |
dc.relation.projectID | Gobierno de España. RD12/0021/0009 | es_ES |
dc.relation.projectID | Gobierno de España. RD16/0009/0016 | es_ES |
dc.relation.projectID | Comunidad de Madrid. S2010/BMD-2321/FIBROTEAM | es_ES |
dc.relation.projectID | Gobierno de España. BES-2013-065986 | es_ES |
dc.relation.projectID | Gobierno de España. BES-2010-035389 | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | en |
dc.rights.cc | Reconocimiento – NoComercial – SinObraDerivada | es_ES |
dc.rights.accessRights | openAccess | en |
dc.authorUAM | Cannata Ortiz, Pablo Javier (271352) | |
dc.authorUAM | Peiró Vallejo, M. Concepción (259003) | |
dc.facultadUAM | Facultad de Medicina | |
dc.institutoUAM | Centro de Biología Molecular Severo Ochoa (CBMSO) | |
dc.institutoUAM | Instituto de Investigación Sanitaria Fundación Jiménez Díaz (ISS-FJD) | |
dc.institutoUAM | Instituto de Investigación Sanitaria Hospital Universitario de La Paz (IdiPAZ) | |