PRDX4 ameliorates oxidative stress-induced injury in endometriosis: potential association with PTP1B oxidation and downstream phosphorylation cascades.

Abstract

Oxidative stress (OS) has been proposed to play a role in the development of endometriosis (EMs). Peroxiredoxins are a family of antioxidant proteins that exhibit peroxidase activity in a thioredoxin-dependent manner, protecting cells against OS. Our previous study has shown that ROS generation is obviously increased in ectopic endometrial stromal cells with inhibition of PRXD4 expression. In our present study, IHC results indicate that the PRDX4 expression was increased in the ectopic endometria of ovarian EMs. Moreover, overexpression of PRDX4 effectively promotes cell migration. In addition, compared with vector group, overexpression of PRDX4 significantly reduces oxidative stress damage induced by H₂O₂, including increased cell viability, decreased intracellular H₂O₂ content, and reduced apoptosis rate. Interestingly, we found that the antioxidation effect of PRDX4 disappeared when the active cysteine residues (Cys124 and Cys245) were replaced with serine. To gain further insight into the antioxidant mechanism of PRDX4, our results shown that overexpression of PRDX4 decreased PTP1B oxidation and phosphorylation cascades. The in vivo findings showed that PRDX4 promoted the growth of ectopic lesions. Taken together, our results indicate that PRDX4 functions as a suppressor in injuries caused by oxidative stress, suggesting that inhibiting PRDX4 expression could be an effective treatment strategy for EMs.