RT Journal Article
T1 Glutathione peroxidase contributes with heme oxygenase-1 to redox balance in mouse brain during the course of cerebral malaria
A1 Linares Gómez, María
A1 Marín-García, Patricia
A1 Martínez-Chacón, Gabriela
A1 Pérez-Benavente, Susana
A1 Puyet Catalina, Antonio
A1 Díez Martín, Amalia
A1 Bautista Santa Cruz, José Manuel
AB Oxidative 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.
PB Elsevier
SN 0925-4439
YR 2013
FD 2013-12
LK https://hdl.handle.net/20.500.14352/93529
UL https://hdl.handle.net/20.500.14352/93529
LA eng
NO Linares 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.
NO Ministerio de Educación y Ciencia (España)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 3 jul 2024