Hydrogen peroxide detoxification through the peroxiredoxin/ thioredoxin antioxidant system: A look at the pancreatic -cell oxidant defense

Reactive oxygen species (ROS), such as hydrogen peroxide, are formed when molecular oxygen obtains additional electrons, increasing its reactivity. While low concentrations of hydrogen peroxide are necessary for regulation of normal cellular signaling events, high concentrations can be toxic. To maintain this balance between beneficial and deleterious concentrations of hydrogen peroxide, cells utilize antioxidants. Our recent work supports a primary role for peroxiredoxin, thioredoxin, and thioredoxin reductase as the oxidant defense pathway used by insulin-producing pancreatic beta-cells. These three players work in an antioxidant cycle based on disulfide exchange, with oxidized targets ultimately being reduced using electrons provided by NADPH. Peroxiredoxins also participate in hydrogen peroxide-based signaling through disulfide exchange with redox-regulated target proteins. This chapter will describe the catalytic mechanisms of thioredoxin, thioredoxin reductase, and peroxiredoxin and provide an in-depth look at the roles these enzymes play in antioxidant defense pathways of insulin-secreting beta-cells. Finally, we will evaluate the physiological relevance of peroxiredoxin-mediated hydrogen peroxide signaling as a regulator of beta-cell function.