EST ablation and estrogen deprivation, respectively, increased and attenuated I/R-responsive Nrf2 accumulation, a potential feedback mechanism to avoid the overactivation of Nrf2.
A–C, female WT, EST−/−, and ovariectomized WT mice were subjected to 60-min/12-h liver I/R. The expression of Nrf2 protein was measured by Western blotting, with the quantification results shown in the right panel (A). Nrf2 target gene expression (B) and EST expression (C) were measured by real-time PCR. n = 4–6; *, p < 0.05; **, p < 0.01. OVX, ovariectomy. D, proposed I/R-responsive and estrogen-EST-Nrf2 mediated feedback mechanism to limit the activity of Nrf2. In this model, Nrf2 induces the expression of EST, which subsequently increases estrogen deactivation and limits the estrogen-responsive induction of Nrf2.