Effect of glycation of hemoglobin on its interaction with trifluoperazine.
Trifluoperazine (TFZ), a phenothiazine drug, penetrates into human erythrocytes and releases oxygen by interaction with hemoglobin. TFZ-induced oxygen release from hyperglycemic erythrocytes isolated from diabetic patients is considerably less compared to that from the cells of normoglycemic individuals. In diabetes mellitus, hemoglobin is significantly glycated by glucose. Non-glycated hemoglobin, HbA0 and its major glycated analog, HbA1c have been separated from the blood samples of diabetic patients. TFZ releases considerable amount of oxygen from HbA0, but very little from HbA1c. Spectrofluorimetric studies reveal that TFZ forms excited state complexes with both HbA0 and HbAlc. Titration of HbA0 with TFZ in a spectrophotometric study exhibits two isosbestic points. Similar experiment with HbAlc causes gradual loss of the Soret peak without appearance of any isosbestic point indicating a possibility of heme loss during interaction, which is also supported by gel filtration experiment and SDS-PAGE experiment followed by heme staining. The results suggest that drug action on hemoglobin is influenced by glycation-induced structural modification of the protein.
Kar
Manoj
M
Department of Biophysics, Molecular Biology & Genetics, University of Calcutta, 92, Acharyya Prafulla Chandra Road, Kolkata 700009, India.
Roy
Anjana
A
Bose
Tania
T
Chakraborti
Abhay Sankar
AS
D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006031:Glycosylation; D006418:Heme / Q000032:analysis; D006441:Hemoglobin A / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D010100:Oxygen / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D014268:Trifluoperazine / Q000378:metabolism* / Q000494:pharmacology*
D006442:Glycated Hemoglobin; D006418:Heme; D006441:Hemoglobin A; D010100:Oxygen; D014268:Trifluoperazine; C028881:hemoglobin A(0)