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 HbA1c. Titration of HbA0 with TFZ in a spectrophotometric study exhibits two isosbestic points. Similar experiment with HbA1c 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.
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Abbreviations
- TFZ:
-
trifluoperazine
- CPZ:
-
chlorpromazine
- HbA0 :
-
non-glycated hemoglobin
- HbA1c :
-
glycated hemoglobin
- TBA:
-
thiobarbituric acid
- PBS:
-
phosphate buffered saline
- SDS-PAGE:
-
sodium dodecyl sulfate-polyacrylamide gel electrophoresis
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Acknowledgements
The study was supported by a grant from the University Grants Commission, New Delhi and one of us (T.B) received a research fellowship from the Commission. Thanks are due to Prof. C. K. DasGupta of this Department and Dr. S. Roy, Department of Biochemistry, University of Calcutta for allowing us to use the Hitachi F-3010 spectrofluorimeter and Gilson 5/6 oxygraph machine, respectively. We are thankful to Prof. U. Chaudhuri of this Department for useful comments and suggestions on the manuscript.
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Kar, M., Roy, A., Bose, T. et al. Effect of Glycation of Hemoglobin on its Interaction with Trifluoperazine. Protein J 25, 202–211 (2006). https://doi.org/10.1007/s10930-006-9003-x
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DOI: https://doi.org/10.1007/s10930-006-9003-x