Induction of Prdx1 and Prdx6 in Liver Cells by Serum and TPA

Peroxiredoxins are thiol-specific antioxidants that protect cells from oxidative damage and have proliferative and anti-apoptotic activity. We investigated the effect of serum and phorbol ester treatment on expression of Prdx1 and Prdx6 in H2.35 cells, and the possible role of Sp1 on Prdx6 induction. Serum stimulation induced a 30% increase in Prdx1 mRNA and a three-fold increase in Prdx6 mRNA. We showed a similar effect of phorbol ester treatment, which led to a 30% increase in Prdx1 mRNA, and over a two-fold increase in Prdx6 expression. Analysis of the Prdx6 proximal promoter sequence revealed four consensus Sp1 sites. Inhibition of Sp1 with mithramycin A blocked Prdx6 induction by TPA and inhibited the serum-induced transcriptional activity of the Prdx6 proximal promoter. These data suggest an important role for Prdx6 in the cellular response to serum and TPA, and implicate Sp1 as a possible mediator of Prdx6 regulation.