Glutathione peroxidase overexpression causes aberrant ERK activation in neonatal mouse cortex after hypoxic preconditioning.

Background: Preconditioning of neonatal mice with nonlethal hypoxia (HPC) protects the brain from hypoxic-ischemic (HI) injury. Overexpression of human glutathione peroxidase 1 (GPx1), which normally protects the developing murine brain from HI injury, reverses HPC protection, suggesting that a certain threshold of hydrogen peroxide concentration is required for activation of HPC signaling.

Methods: Activation (phosphorylation) of extracellular-regulated kinase (ERK) 1/2 and Akt, and induction of hypoxia-inducible factor (HIF)-1α were assessed in the cortex, one of the main structures affected by HI and protected by HPC, at different time points after reoxygenation in wild-type (WT) and GPx1-overexpressing animals.