Oxidative Stress and -Thalassemic Erythroid Cells behind the Molecular Defect
Figure 1
Schematic diagram of abnormalities observed in β-thalassemic red cells. The presence of pathological free iron (Fe) close to the membrane is involved in the Fenton reaction producing reactive oxygen species (ROS, ) contributing to the prooxidant environment of β-thalassemic red cells. The unbalance in α/β chain synthesis results in aggregation of highly oxidative α chains. The prooxidant environment is responsible for protein and lipid oxidative damage favoring abnormal clusterization of red cell membrane proteins such as band 3, promoting band 3 tyrosine phosphorylation (P) and exposure of phosphatidylserine (PS). The abnormally clustered band 3 is recognized by naturally occurring anti-band 3 antibody (IgG). The severely damaged β-thalassemic red cells released microparticles (MPs). The β-thalassemic red cells have short lifespan and are removed by macrophages of the reticuloendothelial systems through PS exposure and IgG anti-band 3 mediated mechanisms. The oxidative stress abnormally activates the K–Cl cotransport (KCC), which promotes K+, Cl−, and water loss contributing to the reduced red cell K+ content that characterizes β-thalassemic red cells.
