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Leishmania amazonensis: Heme stimulates (Na + K)ATPase activity via phosphatidylinositol-specific phospholipase C/protein kinase C-like (PI-PLC/PKC) signaling pathways
Authors:Elmo Eduardo Almeida-Amaral  Fernanda Gomes Francioli
Institution:a Laboratório de Bioquímica Celular, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro - UFRJ, CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil
b Instituto Nacional de Ciência e Tecnologia de Biologia Estrutural e Bioimagem (INCTBEB), CCS, Bloco H, Cidade Universitária, Ilha do Fundão, 21941-590, Rio de Janeiro, RJ, Brazil
c Laboratório de Bioquímica de Tripanosomatideos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz - FIOCRUZ, Pavilhão Leônidas Deane, 4° andar, sala 405, Manguinhos, 21045-900, Rio de Janeiro, RJ, Brazil
Abstract:In the present paper we studied the involvement of the phosphatidylinositol-specific PLC (PI-PLC)/protein kinase C (PKC) pathway in (Na+ + K+)ATPase stimulation by heme in Leishmania amazonensis promastigotes. Heme stimulated the PKC-like activity with a concentration of 50 nM. Interestingly, the maximal stimulation of the PKC-like activity promoted by phorbol ester was of the same magnitude promoted by heme. However, the stimulatory effect of heme is completely abolished by ET-18-OCH3 and U73122, specific inhibitors of PI-PLC. (Na+ + K+)ATPase activity is increased in the presence of increased concentrations of heme, being maximally affected at 50 nM. This effect was completely reversed by 10 nM calphostin C, an inhibitor of PKC. Thus, the effect of 50 nM heme on (Na+ + K+)ATPase activity is completely abolished by ET-18-OCH3 and U73122. Taken together, these results demonstrate that the heme receptor mediates the stimulatory effect of heme on the (Na+ + K+)ATPase activity through a PI-PLC/PKC signaling pathway.
Keywords:Leishmania amazonensis  PKC-like  Heme  (Na+     K+)ATPase  PI-PLC  PI-PLC/PKC signaling pathway
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