Simvastatin activates Keap1/Nrf2 signaling in rat liver

被引：0
作者：
Ioannis G. Habeos
Panos G. Ziros
Dionysios Chartoumpekis
Agathoklis Psyrogiannis
Venetsana Kyriazopoulou
Athanasios G. Papavassiliou
机构：
[1] University of Patras,Department of Internal Medicine, School of Medicine
[2] University of Athens Medical School,Department of Biological Chemistry
来源：
Journal of Molecular Medicine | 2008年 / 86卷
关键词：
GPX2; HO-1; Hepatocyte; Nrf2; Oxidative stress; Simvastatin;
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摘要：
Some of the statins’ pleiotropic actions have been attributed to their antioxidant activity. The Nrf2 transcription factor controls the expression of a number of protective genes in response to oxidative stress. In the present study, wistar rats, primary hepatocytes as well as ST2 cells, were employed to explore the potential role of Nrf2 in mediating the reported antioxidant effects of statins. Simvastatin triggered nuclear translocation of Nrf2 in rat liver and in primary rat hepatocytes in a mevalonate-dependent and cholesterol-independent way. In liver, nuclear extracts from simvastatin-treated rats, the DNA-binding activity of Nrf2, was significantly increased and the mRNA of two known targets of Nrf2 (HO-1 and GPX2) was induced. In ST2 cells stably transfected with constructs bearing Nrf2-binding site (antioxidant responsive element), simvastatin enhanced Nrf2-mediated transcriptional activity in a mevalonate-dependent and cholesterol-independent fashion. In conclusion, activation of Keap1/Nrf2 signaling pathway by simvastatin might provide effective protection of the cell from the deleterious effects of oxidative stress.
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