Heparin binds to Leishmania donovani promastigotes and inhibits protein phosphorylation. |
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| Authors: | N K Mukhopadhyay K Shome A K Saha J R Hassell and R H Glew |
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| Affiliation: | Department of Microbiology, Biochemistry and Molecular Biology, School of Medicine, University of Pittsburgh, PA 15261. |
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| Abstract: | We show that promastigotes of Leishmania donovani, the causative agent of visceral leishmaniasis (kala-azar), possess heparin receptors on their surface. From a linear Scatchard plot of the binding data obtained using 3H]heparin and viable promastigotes, one derives a binding constant of 4.7 x 10(-7) M and an estimate of 860,000 receptors per parasite. The 3H]heparin bound to parasites could not be displaced by hyaluronic acid or by three other glycosaminoglycans (dermatan sulphate, chondroitin 4-sulphate and chondroitin 6-sulphate). It was demonstrated that exponential phase promastigotes growing in medium 199 supplemented with fetal bovine serum incorporate 35SO4 into a cell-associated macromolecule that has the properties of heparin proteoglycan. Heparin inhibits the activity of the cell-surface histone-protein kinase; incubation of viable promastigotes with gamma-32P]ATP and MgCl2 (10 mM) in the absence and presence of heparin (0.01-0.5 mg/ml) for 10 min, followed by analysis by SDS/polyacrylamide-gel electrophoresis and autoradiography, revealed that the phosphorylation of 12 or 13 parasite proteins was inhibited by the glycosaminoglycan. These data suggest that heparin may play a role in the host-parasite relationship. |
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