| First Author | Guo Y | Year | 2015 |
| Journal | J Biol Chem | Volume | 290 |
| Issue | 23 | Pages | 14754-64 |
| PubMed ID | 25922074 | Mgi Jnum | J:315818 |
| Mgi Id | MGI:6831573 | Doi | 10.1074/jbc.M115.642124 |
| Citation | Guo Y, et al. (2015) Estrogen Sulfotransferase Is an Oxidative Stress-responsive Gene That Gender-specifically Affects Liver Ischemia/Reperfusion Injury. J Biol Chem 290(23):14754-64 |
| abstractText | Estrogen sulfotransferase (EST) regulates estrogen homeostasis by sulfonating and deactivating estrogens. Liver ischemia and reperfusion (I/R) involves both hypoxia during the ischemic phase and oxidative damage during the reperfusion phase. In this report, we showed that the expression of EST was markedly induced by I/R. Mechanistically, oxidative stress-induced activation of Nrf2 was responsible for the EST induction, which was abolished in Nrf2(-/-) mice. EST is a direct transcriptional target of Nrf2. In female mice, the I/R-responsive induction of EST compromised estrogen activity. EST ablation attenuated I/R injury as a result of decreased estrogen deprivation, whereas this benefit was abolished upon ovariectomy. The effect of EST ablation was sex-specific because the EST(-/-) males showed heightened I/R injury. Reciprocally, both estrogens and EST regulate the expression and activity of Nrf2. Estrogen deprivation by ovariectomy abolished the I/R-responsive Nrf2 accumulation, whereas the compromised estrogen deprivation in EST(-/-) mice was associated with increased Nrf2 accumulation. Our results suggested a novel I/R-responsive feedback mechanism to limit the activity of Nrf2 in which Nrf2 induces the expression of EST, which subsequently increases estrogen deactivation and limits the estrogen-responsive activation of Nrf2. Inhibition of EST, at least in females, may represent an effective approach to manage hepatic I/R injury. |
