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Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A

Published online by Cambridge University Press:  31 March 2015

PATRICIA L. BUSTOS ,
ALINA E. PERRONE ,
NATALIA MILDUBERGER ,
MIRIAM POSTAN  and
JACQUELINE BUA
PATRICIA L. BUSTOS
Affiliation:
Instituto Nacional de Parasitología “Dr Mario Fatala Chabén”, A.N.L.I.S. Malbrán, Av. Paseo Colón 568, C1063AC S, Buenos Aires, Argentina
ALINA E. PERRONE
Affiliation:
Instituto Nacional de Parasitología “Dr Mario Fatala Chabén”, A.N.L.I.S. Malbrán, Av. Paseo Colón 568, C1063AC S, Buenos Aires, Argentina
NATALIA MILDUBERGER
Affiliation:
Instituto Nacional de Parasitología “Dr Mario Fatala Chabén”, A.N.L.I.S. Malbrán, Av. Paseo Colón 568, C1063AC S, Buenos Aires, Argentina CAECIHS, Universidad Abierta Interamericana, Av. Montes de Oca 745, 2° piso, C1270AAH, Buenos Aires, Argentina
MIRIAM POSTAN
Affiliation:
Instituto Nacional de Parasitología “Dr Mario Fatala Chabén”, A.N.L.I.S. Malbrán, Av. Paseo Colón 568, C1063AC S, Buenos Aires, Argentina
JACQUELINE BUA*
Affiliation:
Instituto Nacional de Parasitología “Dr Mario Fatala Chabén”, A.N.L.I.S. Malbrán, Av. Paseo Colón 568, C1063AC S, Buenos Aires, Argentina CAECIHS, Universidad Abierta Interamericana, Av. Montes de Oca 745, 2° piso, C1270AAH, Buenos Aires, Argentina
*
* Corresponding author. Instituto Nacional de Parasitología “Dr Mario Fatala Chabén”, A.N.L.I.S. Malbrán, Av. Paseo Colón 568, C1063ACS, Ciudad Autónoma de Buenos Aires, Argentina. E-mail: [email protected]
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Summary

Cyclosporin A (CsA) specifically inhibits the mitochondrial permeability transition pore (mPTP). Opening of the mPTP, which is triggered by high levels of matrix [Ca2+] and/or oxidative stress, leads to mitochondrial dysfunction and thus to cell death by either apoptosis or necrosis. In the present study, we analysed the response of Trypanosoma cruzi epimastigote parasites to oxidative stress with 5 mm H2O2, by studying several features related to programmed cell death and the effects of pre-incubation with 1 μ m of CsA. We evaluated TcPARP cleavage, DNA integrity, cytochrome c translocation, Annexin V/propidium iodide staining, reactive oxygen species production. CsA prevented parasite oxidative stress damage as it significantly inhibited DNA degradation, cytochrome c translocation to cytosol and TcPARP cleavage. The calcein-AM/CoCl2 assay, used as a selective indicator of mPTP opening in mammals, was also performed in T. cruzi parasites. H2O2 treatment decreased calcein fluorescence, but this decline was partially inhibited by pre-incubation with CsA. Our results encourage further studies to investigate if there is a mPTP-like pore and a mitochondrial cyclophilin involved in this protozoan parasite.

Keywords

Trypanosoma cruzicyclosporin Aprogrammed cell deathoxidative stresscyclophilin
Type
Research Article
Information
Parasitology , Volume 142 , Issue 8 , July 2015 , pp. 1024 - 1032
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Copyright
Copyright © Cambridge University Press 2015 

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