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Interactions between zinc and NRF2 in vascular redox signalling.
Yang, Fan; Smith, Matthew J; Siow, Richard C M; Aarsland, Dag; Maret, Wolfgang; Mann, Giovanni E.
Afiliación
  • Yang F; School of Cardiovascular and Metabolic Medicine and Sciences, King's British Heart Foundation Centre of Research Excellence, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London SE1 9NH, U.K.
  • Smith MJ; School of Cardiovascular and Metabolic Medicine and Sciences, King's British Heart Foundation Centre of Research Excellence, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London SE1 9NH, U.K.
  • Siow RCM; School of Cardiovascular and Metabolic Medicine and Sciences, King's British Heart Foundation Centre of Research Excellence, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London SE1 9NH, U.K.
  • Aarsland D; Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, U.K.
  • Maret W; Centre for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway.
  • Mann GE; Departments of Biochemistry and Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College, London, U.K.
Biochem Soc Trans ; 52(1): 269-278, 2024 02 28.
Article en En | MEDLINE | ID: mdl-38372426
ABSTRACT
Recent evidence highlights the importance of trace metal micronutrients such as zinc (Zn) in coronary and vascular diseases. Zn2+ plays a signalling role in modulating endothelial nitric oxide synthase and protects the endothelium against oxidative stress by up-regulation of glutathione synthesis. Excessive accumulation of Zn2+ in endothelial cells leads to apoptotic cell death resulting from dysregulation of glutathione and mitochondrial ATP synthesis, whereas zinc deficiency induces an inflammatory phenotype, associated with increased monocyte adhesion. Nuclear factor-E2-related factor 2 (NRF2) is a transcription factor known to target hundreds of different genes. Activation of NRF2 affects redox metabolism, autophagy, cell proliferation, remodelling of the extracellular matrix and wound healing. As a redox-inert metal ion, Zn has emerged as a biomarker in diagnosis and as a therapeutic approach for oxidative-related diseases due to its close link to NRF2 signalling. In non-vascular cell types, Zn has been shown to modify conformations of the NRF2 negative regulators Kelch-like ECH-associated Protein 1 (KEAP1) and glycogen synthase kinase 3ß (GSK3ß) and to promote degradation of BACH1, a transcriptional suppressor of select NRF2 genes. Zn can affect phosphorylation signalling, including mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinases and protein kinase C, which facilitate NRF2 phosphorylation and nuclear translocation. Notably, several NRF2-targeted proteins have been suggested to modify cellular Zn concentration via Zn exporters (ZnTs) and importers (ZIPs) and the Zn buffering protein metallothionein. This review summarises the cross-talk between reactive oxygen species, Zn and NRF2 in antioxidant responses of vascular cells against oxidative stress and hypoxia/reoxygenation.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Zinc / Factor 2 Relacionado con NF-E2 Idioma: En Revista: Biochem Soc Trans Año: 2024 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Zinc / Factor 2 Relacionado con NF-E2 Idioma: En Revista: Biochem Soc Trans Año: 2024 Tipo del documento: Article