TY - JOUR
TI - Simvastatin activates Keap1/Nrf2 signaling in rat liver
AU - Habeos, Ioannis G.
AU - Ziros, Panos G.
AU - Chartoumpekis, Dionysios and
AU - Psyrogiannis, Agathoklis
AU - Kyriazopoulou, Venetsana
AU - Papavassiliou,
AU - Athanasios G.
JO - JOURNAL OF MOLECULAR MEDICINE-JMM
PY - 2008
VL - 86
TODO - 11
SP - 1279-1285
PB - Springer Berlin Heidelberg
SN - null
TODO - 10.1007/s00109-008-0393-4
TODO - GPX2; HO-1; Hepatocyte; Nrf2; Oxidative stress; Simvastatin
TODO - 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.
ER -