title: Trypanosoma brucei brucei: effects of ferrous iron and heme on ecto-nucleoside triphosphate diphosphohydrolase activity.
abstract: 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.
authors.affiliation: Laboratório de Bioquímica Celular, Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, UFRJ, Cidade Universitária, Ilha do Fundão, Rio de Janeiro, Brazil.
authors.forename: Milane S
authors.initials: MS
authors.lastname: Leite
authors.forename: Rachel
authors.initials: R
authors.lastname: Thomaz
authors.forename: José Henrique M
authors.initials: JH
authors.lastname: Oliveira
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Oliveira
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Meyer-Fernandes
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology*; D006418:Heme / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008274:Magnesium / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000187:drug effects* / Q000201:enzymology; D014977:Xanthurenates / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D005296:Ferrous Compounds; D017382:Reactive Oxygen Species; D014977:Xanthurenates; C070295:catalase-polyethylene glycol; D011092:Polyethylene Glycols; D006418:Heme; C028330:xanthurenic acid; D002374:Catalase; D011755:Pyrophosphatases; C021895:nucleoside triphosphate pyrophosphatase; D008274:Magnesium; D000111:Acetylcysteine