Cyclosporin A protects trophoblasts from H2O2-induced oxidative injury via FAK-Src pathway.

Oxidative stress is associated with functional disorder of trophoblast cells. Our previous studies have demonstrated that cyclosporin A (CsA) promotes the activity of normal human trophoblast cells. We further investigated the role and mechanism of CsA on oxidative stress in trophoblast cells. JEG-3 cells were co-cultured with H2O2 and CsA. Cell viability and morphology were measured by MTT assay and inverted microscope. Reactive oxygen species (ROS) was analyzed by fluorescence microscopy. Cell mitochondrial membrane potential (MMP) was determined by flow cytometric analysis. Malondialdehyde (MDA) production, superoxide dismutase (SOD) and catalase (CAT) activities were examined using colorimetric assays. The expression and phosphorylation of FAK and Src kinase proteins were examined by western blotting. CsA increased JEG-3 cell viability and reduced the morphologic injury induced by H2O2 treatment. CsA decreased ROS and MDA production, increased SOD and CAT activities, and restored the MMP of H2O2 treated JEG-3 cells. CsA administration suppressed H2O2-induced reduction of FAK and Src phosphorylation. Blocking the activation of FAK or Src attenuated the protective effect of CsA on JEG-3 cells in H2O2-induced oxidative injury. CsA protects JEG-3 cells from H2O2-induced oxidative injury, and the FAK/Src signaling pathway plays an important role in this process.