Peroxiredoxin 6 protects lung epithelial type II cells against H 2 O 2 ‐induced oxidative stress

Abstract

Peroxiredoxin 6 (Prdx6) is a novel antioxidant enzyme that protects against lung injury associated with oxidative stress. Lung alveolar epithelial type II cells (AECII) play a pivotal role in lung fluid balance, the inflammatory response, and surfactant secretion. The present study investigated the response to H2O2 exposure (50–500 μM for 24 h) of AECII that were isolated from wild type (WT) or Prdx null or transgenic overexpressor (Tg) mouse lungs. H2O2 (250 μM) in WT cells induced Prdx6 protein expression by ~250% during the 24 h treatment period. H2O2 exposure of WT cells resulted in a dose-dependent decrease in cell viability (calcein fluorescence), increased apoptosis (annexin V binding), increased cytotoxicity (propidium iodide uptake), and increased lipid peroxidation (DPPP fluorescence). Prdx6 null cells showed increased cell injury compared to WT cells while overexpressing Tg cells showed protection against these indices of cell injury associated with H2O2 treatment. Thus, deletion of Prdx6 from AECII cells increased their susceptibility to H2O2-induced oxidative stress while Prdx6 overexpression was protective. We propose that Prdx6 protects against cell injury with oxidative stress through its ability to reduce cell membrane lipid hydroperoxides [HL 79063].