It takes 2 antioxidants to tango: the interaction between manganese superoxide dismutase and glutathione peroxidase-1

摘要

Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism. Accumulation of ROS without an effective antioxidant response can lead to oxidative stress, resulting in macromolecular damage that is implicated in the etiology of various diseases including cancer. ROS detoxification is regulated by various antioxidant proteins, specifically manganese superoxide dismutase (MnSOD), which catalyzes the conversion of superoxide into H2O2, and the subsequent conversion of H2O2 into water is catalyzed by glutathione peroxidase 1 (GPx-1). In vitro and in vivo evidence supports a conflicting role of MnSOD in tumor biology and indicates that an interaction between MnSOD and GPx-1 can modulate the impact of MnSOD on carcinogenesis. Additional support for this idea is provided by epidemiological data indicating that an association exists between polymorphisms in the MnSOD and GPx-1 genes and cancer risk, such that individuals who carry both at-risk polymorphisms are at a higher risk of several types of cancer. Future studies examining the impact of these 2 antioxidants on tumor biology need to consider the interplay between the 2 genes.