Protoporphyrin IX-induced structural and functional changes in human red blood cells, haemoglobin and myoglobin.
Protoporphyrin IX and its derivatives are used as photosensitizers in the photodynamic therapy of cancer. Protoporphyrin IX penetrates into human red blood cells and releases oxygen from them. This leads to a change in the morphology of the cells. Spectrophotometric studies reveal that protoporphyrin IX interacts with haemoglobin and myoglobin forming ground state complexes. For both proteins, the binding affinity constant decreases, while the possible number of binding sites increases, as the aggregation state of the porphyrin is increased. The interactions lead to conformational changes of both haemoglobin and myoglobin as observed in circular dichroism studies. Upon binding with the proteins, protoporphyrin IX releases the heme-bound oxygen from the oxyproteins, which is dependent on the stoichiometric ratios of the porphyrin : protein. The peroxidase activities of haemoglobin and myoglobin are potentiated by the protein-porphyrin complexation. Possible mechanisms underlying the relation between the porphyrin-induced structural modifications of the heme proteins and alterations in their functional properties have been discussed. The findings may have a role in establishing efficacy of therapeutic uses of porphyrins as well as in elucidating their mechanisms of action as therapeutic agents.
Sil
Susmita
S
Department of Biophysics, Molecular Biology and Genetics, University College of Science, 92, Acharyya Prafulla Chandra Road, Kolkata 700 009, India.
Bose
Tania
T
Roy
Dibyendu
D
Chakraborti
Abhay Sankar
AS
D000328:Adult; D001665:Binding Sites; D002850:Chromatography, Gel; D002942:Circular Dichroism; D004912:Erythrocytes / Q000378:metabolism*; D006418:Heme / Q000737:chemistry; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D009211:Myoglobin / Q000737:chemistry / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D010544:Peroxidases / Q000378:metabolism; D017319:Photosensitizing Agents / Q000494:pharmacology; D011166:Porphyrins / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011524:Protoporphyrins / Q000737:chemistry* / Q000235:genetics*; D013053:Spectrophotometry; D013997:Time Factors
D006454:Hemoglobins; D009211:Myoglobin; D017319:Photosensitizing Agents; D011166:Porphyrins; D011524:Protoporphyrins; D006418:Heme; C028025:protoporphyrin IX; D010544:Peroxidases; D010100:Oxygen