Oxidative Stress and β-Thalassemic Erythroid Cells behind the Molecular Defect. (24th September 2013) - De Franceschi, Lucia
Abstract : β -thalassemia is a worldwide distributed monogenic red cell disorder, characterized by the absence or reduced β -globin chain synthesis. Despite the extensive knowledge of the molecular defects causing β -thalassemia, less is known about the mechanisms responsible for the associated ineffective erythropoiesis and reduced red cell survival, which sustain anemia of β -thalassemia. The unbalance of alpha-gamma chain and the presence of pathological free iron promote a severe red cell membrane oxidative stress, which results in abnormal β -thalassemic red cell features. These cells are precociously removed by the macrophage system through two mechanisms: the removal of phosphatidylserine positive cells and through the natural occurring antibody produced against the abnormally clustered membrane protein band 3. In the present review we will discuss the changes in β -thalassemic red cell homeostasis related to the oxidative stress and its connection with production of microparticles and with malaria infection. The reactive oxygen species (ROS) are also involved in ineffective erythropoiesis of β -thalassemia through still partially known pathways. Novel cytoprotective systems such as ASHP, eIF2 α, and peroxiredoxin-2 have been suggested to be important against ROS in β -thalassemic erythropoiesis. Finally, we will discuss the results of the major in vitro and in vivo studies with antioxidants in β -thalassemia.