Simvastatin lowers reactive oxygen species level by Nrf2 activation via PI3K/Akt pathway.
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.
Chartoumpekis
Dionysios
D
Department of Internal Medicine, School of Medicine, University of Patras, 26500 Patras, Greece. dchart@upatras.gr
Ziros
Panos G
PG
Psyrogiannis
Agathoklis
A
Kyriazopoulou
Venetsana
V
Papavassiliou
Athanasios G
AG
Habeos
Ioannis G
IG
D000818:Animals; D002460:Cell Line; D005949:Glucose Oxidase / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D019821:Simvastatin / Q000494:pharmacology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D019821:Simvastatin; D005949:Glucose Oxidase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt