Roberta Eitler Bruno

Publications (1)4.09 Total impact

• Source

  Available from: Marcus Oliveira

  Article: Heme-induced ROS in Trypanosoma cruzi activates CaMKII-like that triggers epimastigote proliferation. One helpful effect of ROS.

  Natália Pereira de Almeida Nogueira, Cintia Fernandes de Souza, Francis Monique de Souza Saraiva, Pedro Elias Sultano, Sergio Ranto Dalmau, Roberta Eitler Bruno, Renata de Lima Sales Gonçalves, Gustavo Augusto Travassos Laranja, Luís Henrique Monteiro Leal, Marsen Garcia Pinto Coelho, Claudio A Masuda, Marcus F Oliveira, Marcia Cristina Paes
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  ABSTRACT: Heme is a ubiquitous molecule that has a number of physiological roles. The toxic effects of this molecule have been demonstrated in various models, based on both its pro-oxidant nature and through a detergent mechanism. It is estimated that about 10 mM of heme is released during blood digestion in the blood-sucking bug's midgut. The parasite Trypanosoma cruzi, the agent of Chagas' disease, proliferates in the midgut of the insect vector; however, heme metabolism in trypanosomatids remains to be elucidated. Here we provide a mechanistic explanation for the proliferative effects of heme on trypanosomatids. Heme, but not other porphyrins, induced T. cruzi proliferation, and this phenomenon was accompanied by a marked increase in reactive oxygen species (ROS) formation in epimastigotes when monitored by ROS-sensitive fluorescent probes. Heme-induced ROS production was time- and concentration-dependent. In addition, lipid peroxidation and the formation of 4-hydroxy-2-nonenal (4-HNE) adducts with parasite proteins were increased in epimastigotes in the presence of heme. Conversely, the antioxidants urate and GSH reversed the heme-induced ROS. Urate also decreased parasite proliferation. Among several protein kinase inhibitors tested only specific inhibitors of CaMKII, KN93 and Myr-AIP, were able to abolish heme-induced ROS formation in epimastigotes leading to parasite growth impairment. Taken together, these data provide new insight into T. cruzi- insect vector interactions: heme, a molecule from the blood digestion, triggers epimastigote proliferation through a redox-sensitive signalling mechanism.
  PLoS ONE 01/2011; 6(10):e25935. · 4.09 Impact Factor