Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/129363
COMPARTIR / EXPORTAR:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE

Invitar a revisión por pares abierta
Título

Membrane-bound CYB5R3 is a common effector of nutritional and oxidative stress response through FOXO3a and Nrf2

AutorSiendones, Emilio CSIC; Santa-Cruz Calvo, Sara; Martín-Montalvo, Alejandro CSIC ORCID; Cascajo Almenara, M. V. CSIC ORCID; López-Lluch, Guillermo CSIC ORCID CVN ; Villalba, José M.; Cabo, Rafael de; Navas, Plácido CSIC ORCID
Fecha de publicación2014
EditorMary Ann Liebert
CitaciónAntioxidants and Redox Signaling 21(12): 1708-1725 (2014)
Resumen[Aims]: Membrane-bound CYB5R3 deficiency in humans causes recessive hereditary methaemoglobinaemia (RHM), an incurable disease that is characterized by severe neurological disorders. CYB5R3 encodes for NADH-dependent redox enzyme that contributes to metabolic homeostasis and stress protection; however, how it is involved in the neurological pathology of RHM remains unknown. Here, the role and transcriptional regulation of CYB5R3 was studied under nutritional and oxidative stress. [Results]: CYB5R3-deficient cells exhibited a decrease of the NAD+/NADH ratio, mitochondrial respiration rate, ATP production, and mitochondrial electron transport chain activities, which were associated with higher sensitivity to oxidative stress, and an increase in senescence-associated β-galactosidase activity. Overexpression of either forkhead box class O 3a (FOXO3a) or nuclear factor (erythroid-derived 2)-like2 (Nrf2) was associated with increased CYB5R3 levels, and genetic ablation of Nrf2 resulted in lower CYB5R3 expression. The presence of two antioxidant response element sequences in the CYB5R3 promoter led to chromatin immunoprecipitation studies, which showed that cellular stressors enhanced the binding of Nrf2 and FOXO3a to the CYB5R3 promoter. [Innovation]: Our findings demonstrate that CYB5R3 contributes to regulate redox homeostasis, aerobic metabolism, and cellular senescence, suggesting that CYB5R3 might be a key effector of oxidative and nutritional stress pathways. The expression of CYB5R3 is regulated by the cooperation of Nrf2 and FOXO3a. [Conclusion]: CYB5R3 is an essential gene that appears as a final effector for both nutritional and oxidative stress responses through FOXO3a and Nrf2, respectively, and their interaction promotes CYB5R3 expression. These results unveil a potential mechanism of action by which CYB5R3 deficiency contributes to the pathophysiological underpinnings of neurological disorders in RHM patients.
URIhttp://hdl.handle.net/10261/129363
DOI10.1089/ars.2013.5479
Identificadoresdoi: 10.1089/ars.2013.5479
e-issn: 1557-7716
issn: 1523-0864
Aparece en las colecciones: (CABD) Artículos




Ficheros en este ítem:
Fichero Descripción Tamaño Formato
accesoRestringido.pdf15,38 kBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo

CORE Recommender

PubMed Central
Citations

26
checked on 06-mar-2024

SCOPUSTM   
Citations

34
checked on 22-mar-2024

WEB OF SCIENCETM
Citations

35
checked on 22-feb-2024

Page view(s)

280
checked on 28-mar-2024

Download(s)

96
checked on 28-mar-2024

Google ScholarTM

Check

Altmetric

Altmetric


Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.