Calcineurin B of the human protozoan parasite Trypanosoma cruzi is involved in cell invasion

Calcineurin B of the human protozoan parasite Trypanosoma cruzi is involved in cell invasion

Autor Araya, Jorge E. Google Scholar
Cornejo, Alberto Google Scholar
Orrego, Patricio R. Google Scholar
Cordero, Esteban M. Google Scholar
Cortez, Mauro Google Scholar
Olivares, Hector Google Scholar
Neira, Ivan Google Scholar
Sagua, Hernan Google Scholar
Silveira, Jose Franco da Autor UNIFESP Google Scholar
Yoshida, Nobuko Autor UNIFESP Google Scholar
Gonzalez, Jorge Google Scholar
Instituição Univ Antofagasta
Universidade Federal de São Paulo (UNIFESP)
Resumo During Trypanosoma cruzi cell invasion, signal transduction pathways are triggered in parasite and host cells, leading to a rise in intracellular Ca(2+) concentration. We posed the question whether calcineurin (CaN), in particular the functional regulatory subunit CaNB, a Ca(2+)-binding EF-hand protein, was expressed in T. cruzi and whether it played a role in cell invasion. Here we report the cloning and characterization of CL strain CaNB gene, as well as the participation of CaNB in cell invasion. Treatment of metacyclic trypomastigotes (NIT) or tissue-culture trypomastigotes (TCT) with the CaN inhibitors cyclosporin or cypermethrin strongly inhibited (62-64%) their entry into HeLa cells. in assays using antiphospho-serine/threonine antibodies, a few proteins of MT were found to be dephosphorylated in a manner inhibitable by cyclosporin upon exposure to HeLa cell extract. the phosphatase activity of CaN was detected by a biochemical approach in both MT and TCT. Treatment of parasites with antisense phosphorothioate oligonucleotides directed to TcCaNB-CL, which reduced the expression of TcCaNB and affected TcCaN activity, resulted in similar to 50% inhibition of HeLa cell entry by NIT or TCT. Given that TcCaNB-CL may play a key role in cell invasion and differs considerably in its primary structure from the human CaNB, it might be considered as a potential chemotherapeutic target. (c) 2008 Elsevier Masson SAS. All rights reserved.
Palavra-chave Trypanosoma cruzi
cell invasion
Ca(2+) mobilization
calcincurin B
inhibitors
antisense oligonucleotides
phosphatase activity
Idioma Inglês
Financiador FONDECYT
Fundacion Andes
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Número do financiamento FONDECYT: 1051045
Fundacion Andes: C13955/17
FAPESP: 06/51450-0
Data de publicação 2008-07-01
Publicado em Microbes and Infection. Amsterdam: Elsevier B.V., v. 10, n. 8, p. 892-900, 2008.
ISSN 1286-4579 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 892-900
Fonte http://dx.doi.org/10.1016/j.micinf.2008.05.003
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000259421800007
Endereço permanente http://repositorio.unifesp.br/handle/11600/30763

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