Differential regulation of redox proteins and chaperones in HbEβ‐thalassemia erythrocyte proteome

PURPOSE: In (hemoglobin, Hb) HbEβ-thalassemia, HbE (β-26 Glu→Lys) interacts with β-thalassemia to produce clinical manifestation of varying severity. This is the first proteomic effort to study changes in protein levels of erythrocytes isolated from HbEβ-thalassemic patients compared to normal. EXPERIMENTAL DESIGN: We have used 2-DE and MALDI-MS/MS-based techniques to investigate the differential proteome profiling of membrane and Hb-depleted fraction of cytosolic proteins of erythrocytes isolated from the peripheral blood samples of HbEβ-thalassemia patients and normal volunteers. RESULTS: Our study showed that redox regulators such as peroxiredoxin 2, Cu-Zn superoxide dismutase and thioredoxin and chaperones such as α-hemoglobin stabilizing protein and HSP-70 were upregulated in HbEβ-thalassemia. We have also observed larger amounts of membrane associated globin chains and indications of disruption of spectrin-based junctional complex in the membrane skeleton of HbEβ-thalassemic erythrocytes upon detection of low molecular weight fragments of β-spectrin and decrease in β-actin and dematin content. CONCLUSION AND CLINICAL RELEVANCE: We have observed interesting changes in the proteomic levels of redox regulators and chaperons in the thalassemic hemolysates and have observed strong correlation or association of the extent of such proteomic changes with HbE levels. This could be important in understanding the role of HbE in disease progression and pathophysiology.