Journal
PARASITOLOGY
Volume 142, Issue 8, Pages 1024-1032Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S0031182015000232
Keywords
Trypanosoma cruzi; cyclosporin A; programmed cell death; oxidative stress; cyclophilin
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Funding
- US National Institutes of Health Grant [D43TW00888]
- National Scientific and Technical Research Council (CONICET) Grant [PIP 0317/10]
- ANLIS Carlos G. Malbran and Focanlis [PICTO-ANLIS 00136/11]
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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 mu 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.
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