E Hamilton

Publications (2)6.78 Total impact

• Article: Purine requirements for the expression of Cape buffalo serum trypanocidal activity.

  Q Wang, E Hamilton, S J Black
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  ABSTRACT: Cape buffalo serum contains xanthine oxidase which generates trypanocidal H(2)O(2) during the catabolism of hypoxanthine and xanthine. The present studies show that xanthine oxidase-dependent trypanocidal activity in Cape buffalo serum was also elicited by purine nucleotides, nucleosides, and bases even though xanthine oxidase did not catabolize those purines. The paradox was explained in part, by the presence in serum of purine nucleoside phosphorylase and adenosine deaminase, that, together with xanthine oxidase, catabolized adenosine, inosine, hypoxanthine, and xanthine to uric acid yielding trypanocidal H(2)O(2). In addition, purine catabolism by trypanosomes provided substrates for serum xanthine oxidase and was implicated in the triggering of xanthine oxidase-dependent trypanocidal activity by purines that were not directly catabolized to uric acid in Cape buffalo serum, namely guanosine, guanine, adenine monophosphate, guanosine diphosphate, adenosine 3':5-cyclic monophosphate, and 1-methylinosine. The concentrations of guanosine and guanine that elicited xanthine oxidase-dependent trypanocidal activity were 30-270-fold lower than those of other purines requiring trypanosome-processing which suggests differential processing by the parasites.
  Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology 02/2000; 125(1):25-32. · 2.62 Impact Factor
• Source

  Available from: Samuel J Black

  Article: The trypanocidal Cape buffalo serum protein is xanthine oxidase.

  M Muranjan, Q Wang, Y L Li, E Hamilton, F P Otieno-Omondi, J Wang, A Van Praagh, J G Grootenhuis, S J Black
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  ABSTRACT: Plasma and serum from Cape buffalo (Syncerus caffer) kill bloodstream stages of all species of African trypanosomes in vitro. The trypanocidal serum component was isolated by sequential chromatography on hydroxylapatite, protein A-G, Mono Q, and Superose 12. The purified trypanocidal protein had a molecular mass of 150 kDa, and activity correlated with the presence of a 146-kDa polypeptide detected upon reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Amino acid sequences of three peptide fragments of the 146-kDa reduced polypeptide, ligand affinity and immunoaffinity chromatography of the native protein, and sensitivity to pharmacological inhibitors, identified the trypanocidal material as xanthine oxidase (EC 1.1.3.22). Trypanocidal activity resulted in the inhibition of trypanosome glycolysis and was due to H2O2 produced during catabolism of extracellular xanthine and hypoxanthine by the purine catabolic enzyme.
  Infection and Immunity 10/1997; 65(9):3806-14. · 4.16 Impact Factor