Interaction of hemoglobin and copper nanoparticles: implications in hemoglobinopathy.
Here we study the interaction of copper nanoparticles (CuNPs) with different variants of hemoglobin (Hb). The study reports analysis with HbA0 (the major component of human Hb) and HbA2 (a variant that is associated with beta-thalassemia). In the case of HbA0, the major fraction of human Hb, the CuNPs trigger protein aggregation, and this is followed by the precipitation of the protein. The aggregative response is largely attenuated in the case of HbA2. The difference between the two variants is thus amenable to detection by simple optical methods. We verified that CuNPs co-precipitated with specific Hb variants using atomic absorption spectroscopy (AAS) and high-pressure liquid chromatography (HPLC). An associated observation was the reversal of zeta potential of HbA0 induced by the CuNPs (from -11 mV to +13 mV). Dynamic light-scattering (DLS) studies indicated that in the case of HbA0, protein initially broke the nanoclusters into smaller sizes (4 nm), and this was followed by a gradual increase in cluster size. Assays of heme peroxidase activity indicated that the protein unfolded during the process. It is suggested that interaction between the CuNPs and HbA0 stimulates the molten-globule state of the protein, leading to the onset of such an aggregative pathway. When studied for other variants, HbE, a common mutant of Hb, showed similar aggregative behavior, and on the other hand, rare variants such as HbC tended to remain in solution. A suitable scaling up of the approach may have important implications in screening hemoglobinopathies such as beta-thalassemia.
Bhattacharya
Jaydeep
J
Department of Biochemistry, Calcutta University, Calcutta 700019, India.
Choudhuri
Utpal
U
Siwach
Omprakash
O
Sen
Prasenjit
P
Dasgupta
Anjan Kr
AK
D001665:Binding Sites; D003300:Copper / Q000737:chemistry*; D006453:Hemoglobinopathies / Q000378:metabolism*; D006454:Hemoglobins / Q000737:chemistry* / Q000648:ultrastructure*; D006801:Humans; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure*; D010316:Particle Size; D011485:Protein Binding; D013329:Structure-Activity Relationship
D006454:Hemoglobins; D003300:Copper