Document Detail

Calcineurin B of the human protozoan parasite Trypanosoma cruzi is involved in cell invasion.
MedLine Citation:
PMID:  18657458     Owner:  NLM     Status:  MEDLINE    
During Trypanosoma cruzi cell invasion, signal transduction pathways are triggered in parasite and host cells, leading to a rise in intracellular Ca2+ concentration. We posed the question whether calcineurin (CaN), in particular the functional regulatory subunit CaNB, a Ca2+-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 (MT) or tissue-culture trypomastigotes (TCT) with the CaN inhibitors cyclosporin or cypermethrin strongly inhibited (62-64%) their entry into HeLa cells. In assays using anti-phospho-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 approximately 50% inhibition of HeLa cell entry by MT 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.
Jorge E Araya; Alberto Cornejo; Patricio R Orrego; Esteban M Cordero; Mauro Cortéz; Héctor Olivares; Ivan Neira; Hernán Sagua; José Franco da Silveira; Nobuko Yoshida; Jorge González
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-05-22
Journal Detail:
Title:  Microbes and infection / Institut Pasteur     Volume:  10     ISSN:  1286-4579     ISO Abbreviation:  Microbes Infect.     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-08-11     Completed Date:  2008-10-21     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  100883508     Medline TA:  Microbes Infect     Country:  France    
Other Details:
Languages:  eng     Pagination:  892-900     Citation Subset:  IM    
Molecular Parasitology Unit, Department of Medical Technology, University of Antofagasta, P.O. Box 170, Antofagasta 1240000, Chile.
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MeSH Terms
Amino Acid Sequence
Calcineurin / antagonists & inhibitors,  biosynthesis,  genetics,  physiology*
Cloning, Molecular
Cyclosporine / pharmacology
Enzyme Inhibitors / pharmacology
Gene Silencing
Hela Cells
Molecular Sequence Data
Oligonucleotides, Antisense
Phosphoprotein Phosphatases / antagonists & inhibitors,  biosynthesis,  genetics,  physiology
Protozoan Proteins / biosynthesis,  physiology*
Sequence Alignment
Trypanosoma cruzi / pathogenicity*
Virulence Factors / biosynthesis,  physiology*
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Oligonucleotides, Antisense; 0/Protozoan Proteins; 0/Pyrethrins; 0/Virulence Factors; 52315-07-8/cypermethrin; 59865-13-3/Cyclosporine; EC; EC Phosphatases

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