Journal
EXPERIMENTAL PARASITOLOGY
Volume 124, Issue 4, Pages 436-441Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.exppara.2009.12.012
Keywords
Leishmania amazonensis; PKC-like; Heme; (Na+ + K+)ATPase; PI-PLC; PI-PLC/PKC signaling pathway
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Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Coordenacao de Aperfei oamento de Pessoal de Ensino Superior (CAPES)
- Fundacao Carlos Chagas Filho de Amparo A Pesquisa do Estado do Rio de Janeiro (FAPERJ)
- Fundacao Oswaldo Cruz (FIO-CRUZ)
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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. (C) 2010 Elsevier Inc. All rights reserved.
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