Trypanosoma brucei brucei: Effects of ferrous iron and heme on ecto-nucleoside triphosphate diphosphohydrolase activity

• Published in: Experimental parasitology 2009-02, Vol.121 (2), p.137-143
• Main Authors: Leite, Milane S., Thomaz, Rachel, Oliveira, José Henrique M., Oliveira, Pedro L., Meyer-Fernandes, José Roberto
• Format: Article
• Language: English
• Subjects: Acetylcysteine - pharmacology; Animals; Antioxidants; Antioxidants - pharmacology; apyrase; Biological and medical sciences; catalase; Catalase - pharmacology; Ecto-ATPase; enzyme activity; enzyme inhibition; Ferrous Compounds - pharmacology; Ferrous iron; Fundamental and applied biological sciences. Psychology; Glossina; Heme; Heme - pharmacology; iron; Life cycle. Host-agent relationship. Pathogenesis; lipid peroxidation; Lipid Peroxidation - drug effects; Magnesium - metabolism; Polyethylene Glycols - pharmacology; Procyclic form; procyclic forms; Protozoa; Pyrophosphatases - antagonists & inhibitors; Pyrophosphatases - drug effects; Pyrophosphatases - metabolism; reactive oxygen species; Reactive Oxygen Species - metabolism; Trypanosoma brucei brucei; Trypanosoma brucei brucei - drug effects; Trypanosoma brucei brucei - enzymology; Xanthurenates - pharmacology
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2008.10.018

Trypanosoma brucei brucei is the causative agent of animal African trypanosomiasis, also called nagana. Procyclic vector form resides in the midgut of the tsetse fly, which feeds exclusively on blood. Hemoglobin digestion occurs in the midgut resulting in an intense release of free heme. In the present study we show that the magnesium-dependent ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) activity of procyclic T. brucei brucei is inhibited by ferrous iron and heme. The inhibition of E-NTPDase activity by ferrous iron, but not by heme, was prevented by pre-incubation of cells with catalase. However, antioxidants that permeate cells, such as PEG-catalase and N-acetyl-cysteine prevented the inhibition of E-NTPDase by heme. Ferrous iron was able to induce an increase in lipid peroxidation, while heme did not. Therefore, both ferrous iron and heme can inhibit E-NTPDase activity of T. brucei brucei by means of formation of reactive oxygen species, but apparently acting through distinct mechanisms.