期刊
CHEMICO-BIOLOGICAL INTERACTIONS
卷 195, 期 2, 页码 154-164出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2011.12.005
关键词
Glutathione; Glutathione-related enzymes; Nrf2; p38; Quercetin
资金
- CSIC [2008701198]
- Spanish Ministry of Science and Innovation (CICYT) [AGL2004-302, AGL2007-64042, CSD2007-00063]
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 mu M) for 4 or 18 h induced a differential effect on the modulation of p38 and Nrf2 in HepG2 cells, 50 mu M 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 mu M) 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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