Glutathione peroxidase contributes with heme oxygenase-1 to redox balance in mouse brain during the course of cerebral malaria

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dc.contributor.authorLinares Gómez, María
dc.contributor.authorMarín-García, Patricia
dc.contributor.authorMartínez-Chacón, Gabriela
dc.contributor.authorPérez-Benavente, Susana
dc.contributor.authorPuyet Catalina, Antonio
dc.contributor.authorDíez Martín, Amalia
dc.contributor.authorBautista Santa Cruz, José Manuel
dc.date.accessioned2024-01-17T09:13:28Z
dc.date.available2024-01-17T09:13:28Z
dc.date.issued2013-12
dc.description.abstractOxidative stress has been attributed both a key pathogenic and rescuing role in cerebral malaria (CM). In a Plasmodium berghei ANKA murine model of CM, host redox signaling and functioning were examined during the course of neurological damage. Host antioxidant defenses were early altered at the transcriptional level indicated by the gradually diminished expression of superoxide dismutase-1 (sod-1), sod-2, sod-3 and catalase genes. During severe disease, this led to the dysfunctional activity of superoxide dismutase and catalase enzymes in damaged brain regions. Vitagene associated markers (heat shock protein 70 and thioredoxin-1) also showed a decaying expression pattern that paralleled reduced expression of the transcription factors Parkinson disease 7, Forkhead box O 3 and X-box binding protein 1 with a role in preserving brain redox status. However, the oxidative stress markers reactive oxygen/nitrogen species were not accumulated in the brains of CM mice and redox proteomics and immunohistochemistry failed to detect quantitative or qualitative differences in protein carbonylation. Thus, the loss of antioxidant capacity was compensated for in all cerebral regions by progressive upregulation of heme oxygenase-1, and in specific regions by early glutathione peroxidase-1 induction. This study shows for the first time a scenario of cooperative glutathione peroxidase and heme oxygenase-1 upregulation to suppress superoxide dismutase, catalase, heat shock protein-70 and thioredoxin-1 downregulation effects in experimental CM, counteracting oxidative damage and maintaining redox equilibrium. Our findings reconcile the apparent inconsistency between the lack of oxidative metabolite build up and reported protective effect of antioxidant therapy against CM.eng
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Educación y Ciencia (España)
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.statuspub
dc.identifier.citationLinares M, Marín-García P, Martínez-Chacón G, Pérez-Benavente S, Puyet A, Diez A, et al. Glutathione peroxidase contributes with heme oxygenase-1 to redox balance in mouse brain during the course of cerebral malaria. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2013;1832:2009–18. https://doi.org/10.1016/j.bbadis.2013.07.010.
dc.identifier.doi10.1016/j.bbadis.2013.07.010
dc.identifier.essn1879-260X
dc.identifier.issn0925-4439
dc.identifier.officialurlhttps://doi.org/10.1016/j.bbadis.2013.07.010
dc.identifier.urihttps://hdl.handle.net/20.500.14352/93529
dc.issue.number12
dc.journal.titleBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
dc.language.isoeng
dc.page.final2018
dc.page.initial2009
dc.publisherElsevier
dc.relation.projectIDinfo:eu-repo/grantAgreement/BIO2010-17039
dc.relation.projectIDinfo:eu-repo/grantAgreement/AP20061576
dc.rights.accessRightsrestricted access
dc.subject.keywordOxidative stress
dc.subject.keywordExperimental cerebral malaria
dc.subject.keywordRedox proteomics
dc.subject.keywordRedox balance
dc.subject.ucmCiencias Biomédicas
dc.subject.unesco24 Ciencias de la Vida
dc.titleGlutathione peroxidase contributes with heme oxygenase-1 to redox balance in mouse brain during the course of cerebral malaria
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number1832
dspace.entity.typePublication
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relation.isAuthorOfPublication.latestForDiscovery855e6962-3ee2-4fc3-b110-96f1c20c5269
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