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Heme-induced Trypanosoma cruzi proliferation is mediated by CaM kinase II
Authors:CF Souza  AB Silveira  MAC Silva-Neto  SC Gonçalves da Costa
Institution:a Laboratório de Interação Tripanosomatídeos e Vetores, Departamento de Bioquímica, IBRAG, UERJ, 20551-030 Rio de Janeiro, Brazil
b Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fiocruz, Brazil
c Laboratório de Sinalização Celular, Instituto de Bioquímica Médica, UFRJ, Brazil
d INCT, Entomologia Molecular, Brazil
Abstract:Trypanosoma cruzi, the etiologic agent of Chagas disease, is transmitted through triatomine vectors during their blood-meal on vertebrate hosts. These hematophagous insects usually ingest approximately 10 mM of heme bound to hemoglobin in a single meal. Blood forms of the parasite are transformed into epimastigotes in the crop which initiates a few hours after parasite ingestion. In a previous work, we investigated the role of heme in parasite cell proliferation and showed that the addition of heme significantly increased parasite proliferation in a dose-dependent manner 1]. To investigate whether the heme effect is mediated by protein kinase signalling pathways, parasite proliferation was evaluated in the presence of several protein kinase (PK) inhibitors. We found that only KN-93, a classical inhibitor of calcium-calmodulin-dependent kinases (CaMKs), blocked heme-induced cell proliferation. KN-92, an inactive analogue of KN-93, was not able to block this effect. A T. cruzi CaMKII homologue is most likely the main enzyme involved in this process since parasite proliferation was also blocked when Myr-AIP, an inhibitory peptide for mammalian CaMKII, was included in the cell proliferation assay. Moreover, CaMK activity increased in parasite cells with the addition of heme as shown by immunological and biochemical assays. In conclusion, the present results are the first strong indications that CaMKII is involved in the heme-induced cell signalling pathway that mediates parasite proliferation.
Keywords:Heme  Trypanosoma cruzi  Ca2+/calmodulin kinase II
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