Hydrogen peroxide contributes to the manganese superoxide dismutase promotion of migration and invasion in glioma cells

Manganese superoxide dismutase (MnSOD) is over-expressed in most brain tumours, and high MnSOD expression is associated with poor prognosis. The mechanisms still remain largely unknown. In the present study, the elevation of hydrogen peroxide (H2O2) level and the enhancement of glioma migration/invasion by over-expression of MnSOD were demonstrated. Subsequent studies showed that over-expression of MnSOD significantly increased the activation of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinases (PI3Ks), including AKTs, s6-ribosomal protein, ERKs and JNKs. Over-expression of MnSOD was also associated with elevations of matrix metalloproteinases-1(MMP-1) and MMP-9 protein. The promotion of migration/invasion, activation of PI3Ks and MAPKs and up-regulation of MMPs were inhibited by the general reactive oxygen species scavenger N-acetyl-l-cysteine (NAC), over-expression of the H2O2-detoxifying enzyme mitochondrial catalase (mCat) and specific inhibitors of AKTs or ERKs. Collectively, our study indicated that H2O2 would contribute to the MnSOD-promoted migration/invasion in glioma cells through activation of AKTs and ERKs. This study provided new molecular insights into the understanding of glioma migration and invasion.