Activation of HO-1 protects placental cells function in oxidative stress via regulating ZO-1/occludin

Abstract

We previously confirmed that Nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase (HO-1) play synergistic roles in the pathogenesis of preeclampsia. To further explore the function of HO-1 in the pathogenesis of preeclampsia, we established oxidative stress models respectively with human first-trimester trophoblast/simian virus (HTR8/SVneo) and human umbilical vein endothelial cells (HUVECs) and then assessed the effect of HO-1 on the two cell lines in oxidative stress conditions. The cell oxidative stress models were incubated with Hemin (an inducer of HO-1), then, the HTR8/SVneo cells were transfected by ZO-1 small interfering RNA (siRNA). The HTR-8/SVneo invasive abilities were detected, and the tube formation abilities of HUVECs were measured. HO-1 and tight junction proteins zonula occludens-1 (ZO-1) and occludin in the cells were detected. In both the trophoblastic and HUVEC oxidative stress models, HO-1、ZO-1 and occludin were increased incubated with Hemin. Meanwhile, HTR-8/SVneo cells incubated with Hemin showed increased invasion function against the destruction of hydrogen peroxide (H2O2). Similarly, the tube formation ability of HUVECs incubated with Hemin was increased. The above-mentioned effects were disappeared after HTR-8/SVneo cells were transfected by ZO-1 siRNA. These results suggest that HO-1 protects the function of placental cells in oxidative stress via regulating ZO-1/occludin.