Effects of free soluble iron on thermal aggregation of hemoglobin

Aggregation of hemoglobin is implicated in the presentation of diseases like sickle cell disease and thalassemia. Hallmark of the disease being imbalance in the production of globin chains leading to aggregation of excess globin chains and aberrant hemoglobins associated with the disease, broadly categorized as hemoglobinopathy. We have studied thermal aggregation of hemoglobin at 70 °C and pH 6.5 using light scattering, flow cytometry and optical microscopy and tried to investigate effects of few abundant soluble metal ions on such aggregation. Our study indicate that only iron, both in Fe²⁺ and Fe³⁺ forms, could inhibit hemoglobin aggregation and the extent of inhibition was 60% in presence of 100 mgL^-1 FeCl₃. Similar effect was not seen in lysozyme aggregation. Metal ions such as, Cu²⁺, Zn²⁺ and Ni²⁺ also did not have any significant effects on hemoglobin aggregation. Results show this important chaperone like behavior of free iron affecting the kinetics and yield of the aggregation process which could have important consequence in the extent of severity of such hematological diseases.