Protection of l-methionine against H2O2-induced oxidative damage in mitochondria

Reactive oxygen species (ROS) is reported to be a critical pathogenic factor and mitochondria is one of the susceptible subcellular organs for oxidative damage. Methionine sulfoxide reductase A (MsrA) is a key anti-oxidant enzyme associated with cytoprotection and previous reports have revealed its importance in mitochondrial function. The anti-oxidation of MsrA is due to Met-centered redox cycle, suggesting that Met-centered redox cycle may play a critical role in mitochondrial protection. l-Methionine (l-Met), a natural amino acid with anti-oxidation activity, can mimic the effect of Met-centered redox cycle. Here, we investigated the protection of l-Met on H2O2-induced oxidative damage in mitochondria. Our study demonstrated that l-Met protected H2O2-induced injury in CHO cells. Cytoprotections of l-Met at low concentrations (1-5 mM) were abolished by dimethyl sulfoxide (DMSO), a competitive inhibitor of MsrA function, suggesting that these effects may involve the participation of MsrA. Overexpression of MsrA in CHO cells protected mitochondria from H2O2-induced downtrend of membrane potential and production of mitochondrial superoxide. Pre-treatment with l-Met (1 mM) produced a similar effect on the mitochondrial protection against H2O2. Furthermore, it was observed that topical application of l-Met can prevent 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced oxidative damage in the skin of mice. These results suggest that anti-oxidation activity of l-Met may promise a new strategy for the prevention of oxidative stress-induced damage.

► MsrA protects against oxidative stress-induced toxicology in mitochondrial. ► l-Met protects mitochondria from oxidative stress-induced damage. ► l-Met protects oxidant-induced cytotoxicology via a MsrA-dependent pathway.