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Title: Calcineurin B of the human protozoan parasite Trypanosoma cruzi is involved in cell invasion
Authors: Araya, Jorge E.
Cornejo, Alberto
Orrego, Patricio R.
Cordero, Esteban M.
Cortez, Mauro
Olivares, Hector
Neira, Ivan
Sagua, Hernan
Silveira, Jose Franco da [UNIFESP]
Yoshida, Nobuko [UNIFESP]
Gonzalez, Jorge
Univ Antofagasta
Universidade Federal de São Paulo (UNIFESP)
Keywords: Trypanosoma cruzi
cell invasion
Ca(2+) mobilization
calcincurin B
antisense oligonucleotides
phosphatase activity
Issue Date: 1-Jul-2008
Publisher: Elsevier B.V.
Citation: Microbes and Infection. Amsterdam: Elsevier B.V., v. 10, n. 8, p. 892-900, 2008.
Abstract: 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.
ISSN: 1286-4579
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