Simvastatin lowers reactive oxygen species level by Nrf2 activation via PI3K/Akt pathway |
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| Authors: | Dionysios Chartoumpekis Panos G. Ziros Agathoklis Psyrogiannis |
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| Affiliation: | a Department of Internal Medicine, School of Medicine, University of Patras, 26500 Patras, Greece
b Department of Biological Chemistry, University of Athens Medical School, 11527 Athens, Greece |
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| Abstract: | The beneficial effects of HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase inhibitors (statins) have been attributed not only to their cholesterol lowering effect but also to their pleiotropic actions and especially to their anti-oxidant activity. Nrf2 (NF-E2-related factor 2) is a transcription factor that orchestrates the transcriptional response of cells to oxidative stressors and electrophilic xenobiotics. In this study, primary mouse embryonic fibroblasts from wild type or Nrf2 knock out C57BL6J mice and ST-2 cells were used to investigate the implication of Nrf2 in the mediation of the anti-oxidant effects of statins and the possible involvement of PI3K/Akt pathway in this process. We show for the first time that simvastatin lowers reactive oxygen species (ROS) by activating Nrf2 through the PI3K/Akt pathway. |
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| Keywords: | HMG-CoA, 3-hydroxy-3-methyl-glutaryl-CoA Nrf2, NF-E2-related factor 2 ROS, reactive oxygen species Keap1, Kelch-like ECH associating protein ARE, antioxidant response element FBS, fetal bovine serum MEF, mouse embryonic fibroblast WT, wild type KO, knock out CM-H2DCFDA, 5-(and-6)-chloromethyl-2&prime 7&prime -dichlorodihydrofluorescein diacetate acetyl ester |
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