title: The heme uptake process in Trypanosoma cruzi epimastigotes is inhibited by heme analogues and by inhibitors of ABC transporters.
abstract: Heme (iron protoporphyrin IX) is an important molecule involved in many biological reactions, including oxygen transport, respiration, photosynthesis and drug detoxification. Trypanosoma cruzi parasites, the etiological agent of Chagas' disease, take up heme from the environment to supply their nutritional needs because they do not synthesize this cofactor. However, the mechanisms involved in heme transport across biological membranes are poorly understood. Indeed, in T. cruzi, no heme transporter has yet been characterized. In the present work, we evaluate the heme uptake processes by T. cruzi epimastigotes using fluorescent heme-analogues. Heme uptake decreased significantly when cells were pretreated with different concentrations of SnPPIX, PdMPIX or ZnMPIX, this observed competition suggests that they are taken up by the same transport system. We studied the growth behavior of epimastigotes using the same heme-analogues and the treatments with SnPPIX or PdMPIX impaired cell growth but when heme was added to the culture medium the observed inhibition was partially reversed. In addition, we tested how the heme uptake processes are affected by the presence of different transporter inhibitors. When the cells were treated with inhibitors and then incubated with heme, heme uptake decreased significantly for all treatments. These results constitute a strong indication for the existence of a protein associated with porphyrin transport in T. cruzi, possibly ATP-binding cassette transporters (ABC-transporter).
authors: Laboratório de Interação Tripanossomatídeos e Vetores, Departamento de Bioquímica, Instituto de Biologia Roberto Alcântara Gomes, IBRAG, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Mauricio Peixoto
authors: MP
authors: Cupello
authors: Cíntia Fernandes de
authors: CF
authors: Souza
authors: Celeste
authors: C
authors: Buchensky
authors: Juliana Baptista Rocha Corrêa
authors: JB
authors: Soares
authors: Gustavo Augusto Travassos
authors: GA
authors: Laranja
authors: Marsen Garcia Pinto
authors: MG
authors: Coelho
authors: Julia A
authors: JA
authors: Cricco
authors: Marcia Cristina
authors: MC
authors: Paes
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D001692:Biological Transport; D003470:Culture Media / Q000737:chemistry; D006418:Heme / Q000031:analogs & derivatives / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000254:growth & development / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D003470:Culture Media; D006418:Heme