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

Abstract

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.

Keywords::

• ROS
• superoxide
• MnSOD
• hydrogen peroxide
• glioma
• invasion
• migration
• superoxide dismutase
• signal transduction
• brain

This paper was first published online on Early Online on 5 August 2011.