%0 Journal Article
%T Oxidative Stress and -Thalassemic Erythroid Cells behind the Molecular Defect
%A Lucia De Franceschi
%A Mariarita Bertoldi
%A Alessandro Matte
%A Sara Santos Franco
%A Antonella Pantaleo
%A Emanuela Ferru
%A Franco Turrini
%J Oxidative Medicine and Cellular Longevity
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/985210
%X ¦Â-thalassemia is a worldwide distributed monogenic red cell disorder, characterized by the absence or reduced ¦Â-globin chain synthesis. Despite the extensive knowledge of the molecular defects causing ¦Â-thalassemia, less is known about the mechanisms responsible for the associated ineffective erythropoiesis and reduced red cell survival, which sustain anemia of ¦Â-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 ¦Â-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 ¦Â-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 ¦Â-thalassemia through still partially known pathways. Novel cytoprotective systems such as ASHP, eIF2¦Á, and peroxiredoxin-2 have been suggested to be important against ROS in ¦Â-thalassemic erythropoiesis. Finally, we will discuss the results of the major in vitro and in vivo studies with antioxidants in ¦Â-thalassemia. 1. Introduction The World Health Organization has identified the hereditary red cell disorders as emerging diseases with high impact on public health systems in both Western and developing countries. Approximately 7% of the global population is carrier of such disorders, and 300,000¨C400,000 babies with severe forms of these diseases are born each year [1¨C3]. Severe hereditary hemoglobin disorders of red cells occur at highest frequency in tropical regions, but pop0ulation migrations have ensured that they are present and growing in prevalence in most Western countries. Hemoglobinopathies constitute the single most common monogenic defect worldwide, and among hemoglobin disorders, the thalassemias prominently contribute to [1¨C4]. ¦Â-thalassemias (¦Â-thal) are characterized by the presence of mutations on beta-globin gene resulting in the absence or reduced synthesis of ¦Â-globin chains. This is responsible for unbalance in globin chain synthesis with unpaired ¦Á-chains aggregation. Despite the extensive knowledge of the molecular defects causing ¦Â-thalassemia, less is known about the mechanisms responsible for the associated ineffective erythropoiesis and reduced
%U http://www.hindawi.com/journals/omcl/2013/985210/