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Activation of glutathione peroxidase via Nrf1 mediates genistein's protection against oxidative endothelial cell injury

Hernandez-Montes, E., Pollard, S.E., Vauzour, D., Jofre-Montseny, L., Rota, C., Rimbach, G., Weinberg, P.D. and Spencer, J.P.E. ORCID: https://orcid.org/0000-0003-2931-7274 (2006) Activation of glutathione peroxidase via Nrf1 mediates genistein's protection against oxidative endothelial cell injury. Biochemical and Biophysical Research Communications, 346 (3). pp. 851-859. ISSN 0006-291X

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To link to this item DOI: 10.1016/j.bbrc.2006.05.197

Abstract/Summary

Cellular actions of isoflavones may mediate the beneficial health effects associated with high soy consumption. We have investigated protection by genistein and daidzein against oxidative stress-induced endothelial injury. Genistein but not daidzein protected endothelial cells from damage induced by oxidative stress. This protection was accompanied by decreases in intracellular glutathione levels that could be explained by the generation of glutathionyl conjugates of the oxidised genistein metabolite, 5,7,3',4'-tetrahydroxyisoflavone. Both isoflavones evoked increased protein expression of gamma-glutamylcysteine synthetase-heavy subunit (gamma-GCS-HS) and increased cytosolic accumulation and nuclear translocation of Nrf2. However, only genistein led to increases in the cytosolic accumulation and nuclear translocation of Nrf1 and the increased expression of and activity of glutathione peroxidase. These results suggest that genistein-induced protective effects depend primarily on the activation of glutathione peroxidase mediated by Nrf1 activation, and not on Nrf2 activation or increases in glutathione synthesis. (c) 2006 Elsevier Inc. All rights reserved.

Item Type:Article
Refereed:Yes
Divisions:Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences
Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
ID Code:13318
Uncontrolled Keywords:isoflavone, genistein, metabolism, glutathione peroxidase, Nrf1, Nrf2, gamma-glutamylcysteine synthetase, oxidative stress, endothelial cell, GAMMA-GLUTAMYLCYSTEINE SYNTHETASE, IN-VIVO METABOLITES, PHASE-II, ENZYMES, FACTOR-KAPPA-B, MOLECULAR-MECHANISM, DIETARY POLYPHENOLS, SUBUNIT PROMOTER, HEAVY SUBUNIT, NITRIC-OXIDE, BLACK TEA

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