Activation of glutathione peroxidase via Nrf1 mediates genistein's protection against oxidative endothelial cell injury
- Molecular Nutrition Group, School of Chemistry, Food Biosciences and Pharmacy, University of Reading, Reading RG6 6AP (United Kingdom)
- University of Kiel, Christian Albrechts University, Institute of Human Nutrition and Food Science, Olshausenstrasse 40, D-24098 Kiel (Germany)
- Universita di Modena e Reggio Emilia, Dipartimento di Scienze Biomediche, Via Campi 287, 41100 Modena (Italy)
- Department of Bioengineering, Imperial College, London SW7 2AZ (United Kingdom)
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.
- OSTI ID:
- 20854391
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 346, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2006.05.197; PII: S0006-291X(06)01261-7; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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