Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38
Dietary flavonoid quercetin has been suggested as a cancer chemopreventive agent, but the mechanisms of action remain unclear. This study investigated the influence of quercetin on p38-MAPK and the potential regulation of the nuclear transcription factor erythroid-2p45-related factor (Nrf2) and the cellular antioxidant/detoxifying defense system related to glutathione (GSH) by p38 in HepG2 cells. Incubation of HepG2 cells with quercetin at a range of concentrations (5-50 οM) for 4 or 18 h induced a differential effect on the modulation of p38 and Nrf2 in HepG2 cells, 50 οM quercetin showed the highest activation of p38 at 4h of treatment and values of p38 similar to those of control cells after 18 h of incubation, together with the inhibition of Nrf2 at both incubation times. Quercetin (50 οM) induced a time-dependent activation of p38, which was in concert with a transient stimulation of Nrf2 to provoke its inhibition afterward. Quercetin also increased GSH content, mRNA levels of glutamylcysteine-synthetase (GCS) and expression and/or activity of glutathione-peroxidase, glutathione-reductase and GCS after 4 h of incubation, and glutathione-S-transferase after 18 h of exposure. Further studies with the p38 specific inhibitor SB203580 showed that the p38 blockage restored the inhibited Nrf2 transcription factor and the enzymatic expression and activity of antioxidant/detoxificant enzymes after 4 h exposure. In conclusion, p38-MAPK is involved in the mechanisms of the cell response to quercetin through the modulation of Nrf2 and glutathione-related enzymes in HepG2 cells. © 2011 Elsevier Ireland Ltd. All rights reserved.
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dig-ictan-es-10261-607092022-01-26T09:09:56Z Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38 Granado-Serrano, Ana B. Martín, M. Ángeles Bravo, Laura Goya, Luis Ramos, Sonia Ministerio de Ciencia e Innovación (España) Ministerio de Educación y Ciencia (España) Dietary flavonoid quercetin has been suggested as a cancer chemopreventive agent, but the mechanisms of action remain unclear. This study investigated the influence of quercetin on p38-MAPK and the potential regulation of the nuclear transcription factor erythroid-2p45-related factor (Nrf2) and the cellular antioxidant/detoxifying defense system related to glutathione (GSH) by p38 in HepG2 cells. Incubation of HepG2 cells with quercetin at a range of concentrations (5-50 οM) for 4 or 18 h induced a differential effect on the modulation of p38 and Nrf2 in HepG2 cells, 50 οM quercetin showed the highest activation of p38 at 4h of treatment and values of p38 similar to those of control cells after 18 h of incubation, together with the inhibition of Nrf2 at both incubation times. Quercetin (50 οM) induced a time-dependent activation of p38, which was in concert with a transient stimulation of Nrf2 to provoke its inhibition afterward. Quercetin also increased GSH content, mRNA levels of glutamylcysteine-synthetase (GCS) and expression and/or activity of glutathione-peroxidase, glutathione-reductase and GCS after 4 h of incubation, and glutathione-S-transferase after 18 h of exposure. Further studies with the p38 specific inhibitor SB203580 showed that the p38 blockage restored the inhibited Nrf2 transcription factor and the enzymatic expression and activity of antioxidant/detoxificant enzymes after 4 h exposure. In conclusion, p38-MAPK is involved in the mechanisms of the cell response to quercetin through the modulation of Nrf2 and glutathione-related enzymes in HepG2 cells. © 2011 Elsevier Ireland Ltd. All rights reserved. This work was supported by the Grants 200870I198 (CSIC), and AGL2004-302, AGL2007-64042 and CSD2007-00063 from the Spanish Ministry of Science and Innovation (CICYT). A.B. Granado-Serrano was a predoctoral fellow of the Spanish Ministry of Science and Education. Peer Reviewed 2012-11-21T10:14:23Z 2012-11-21T10:14:23Z 2012 2012-11-21T10:14:23Z artículo http://purl.org/coar/resource_type/c_6501 doi: 10.1016/j.cbi.2011.12.005 issn: 0009-2797 Chemico-Biological Interactions 195(2): 154-164 (2012) http://hdl.handle.net/10261/60709 10.1016/j.cbi.2011.12.005 http://dx.doi.org/10.13039/501100004837 22197970 en Postprint https://doi.org/10.1016/j.cbi.2011.12.005 open Elsevier |
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Dietary flavonoid quercetin has been suggested as a cancer chemopreventive agent, but the mechanisms of action remain unclear. This study investigated the influence of quercetin on p38-MAPK and the potential regulation of the nuclear transcription factor erythroid-2p45-related factor (Nrf2) and the cellular antioxidant/detoxifying defense system related to glutathione (GSH) by p38 in HepG2 cells. Incubation of HepG2 cells with quercetin at a range of concentrations (5-50 οM) for 4 or 18 h induced a differential effect on the modulation of p38 and Nrf2 in HepG2 cells, 50 οM quercetin showed the highest activation of p38 at 4h of treatment and values of p38 similar to those of control cells after 18 h of incubation, together with the inhibition of Nrf2 at both incubation times. Quercetin (50 οM) induced a time-dependent activation of p38, which was in concert with a transient stimulation of Nrf2 to provoke its inhibition afterward. Quercetin also increased GSH content, mRNA levels of glutamylcysteine-synthetase (GCS) and expression and/or activity of glutathione-peroxidase, glutathione-reductase and GCS after 4 h of incubation, and glutathione-S-transferase after 18 h of exposure. Further studies with the p38 specific inhibitor SB203580 showed that the p38 blockage restored the inhibited Nrf2 transcription factor and the enzymatic expression and activity of antioxidant/detoxificant enzymes after 4 h exposure. In conclusion, p38-MAPK is involved in the mechanisms of the cell response to quercetin through the modulation of Nrf2 and glutathione-related enzymes in HepG2 cells. © 2011 Elsevier Ireland Ltd. All rights reserved. |
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Ministerio de Ciencia e Innovación (España) |
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Ministerio de Ciencia e Innovación (España) Granado-Serrano, Ana B. Martín, M. Ángeles Bravo, Laura Goya, Luis Ramos, Sonia |
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Granado-Serrano, Ana B. Martín, M. Ángeles Bravo, Laura Goya, Luis Ramos, Sonia |
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Granado-Serrano, Ana B. Martín, M. Ángeles Bravo, Laura Goya, Luis Ramos, Sonia Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38 |
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Granado-Serrano, Ana B. |
title |
Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38 |
title_short |
Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38 |
title_full |
Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38 |
title_fullStr |
Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38 |
title_full_unstemmed |
Quercetin modulates Nrf2 and glutathione-related defenses in HepG2 cells: Involvement of p38 |
title_sort |
quercetin modulates nrf2 and glutathione-related defenses in hepg2 cells: involvement of p38 |
publisher |
Elsevier |
publishDate |
2012 |
url |
http://hdl.handle.net/10261/60709 http://dx.doi.org/10.13039/501100004837 |
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