Redox biology from the perspective of the red blood cell

Decades of research have generated extensive knowledge on oxidant production and antioxidant systems in red blood cells. This work has given us not only a detailed understanding of redox control in these cells but also fundamental information that has helped shape the broader field of redox biology. This review covers aspects of this history and also highlights unresolved issues regarding erythrocyte antioxidant defenses. Hemoglobin is both the principal source of reactive oxidants, produced by autoxidation or interaction with redox-active xenobiotics, and a major target of oxidants that escape the antioxidant network. Antioxidant protection requires an ongoing supply of NADPH without which, as in glucose-6-phosphate dehydrogenase deficiency, the cells are predisposed to oxidant drug-induced hemoglobin oxidation and hemolyic anemia. Red cells express high concentrations of superoxide dismutase, catalase, and multiple peroxiredoxins and glutathione peroxidases. We review likely contributions of these systems to hydrogen peroxide removal and highlight uncertainties about their apparent redundancy. Catalase and superoxide dismutase are enigmatic. Physiological conditions under which catalase supplants peroxiredoxins for hydrogen peroxide removal appear to be rare. Likewise, a role for superoxide dismutase in red cells is elusive as the reactions of superoxide considered to be toxic to other cells should be limited. Thus, fundamental questions still need to be resolved.