title: Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A.
abstract: 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.
authors.affiliation: Instituto Nacional de Parasitología "Dr Mario Fatala Chabén",A.N.L.I.S. Malbrán,Av. Paseo Colón 568,C1063AC S,Buenos Aires,Argentina.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Bustos
authors.affiliation: Instituto Nacional de Parasitología "Dr Mario Fatala Chabén",A.N.L.I.S. Malbrán,Av. Paseo Colón 568,C1063AC S,Buenos Aires,Argentina.
authors.forename: Alina E
authors.initials: AE
authors.lastname: Perrone
authors.affiliation: Instituto Nacional de Parasitología "Dr Mario Fatala Chabén",A.N.L.I.S. Malbrán,Av. Paseo Colón 568,C1063AC S,Buenos Aires,Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Milduberger
authors.affiliation: Instituto Nacional de Parasitología "Dr Mario Fatala Chabén",A.N.L.I.S. Malbrán,Av. Paseo Colón 568,C1063AC S,Buenos Aires,Argentina.
authors.forename: Miriam
authors.initials: M
authors.lastname: Postan
authors.affiliation: Instituto Nacional de Parasitología "Dr Mario Fatala Chabén",A.N.L.I.S. Malbrán,Av. Paseo Colón 568,C1063AC S,Buenos Aires,Argentina.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Bua
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D065095:Calcineurin Inhibitors / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D021983:Cyclophilins / Q000037:antagonists & inhibitors; D016572:Cyclosporine / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D005452:Fluoresceins; D005456:Fluorescent Dyes; D006861:Hydrogen Peroxide / Q000009:adverse effects; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D000083162:Mitochondrial Permeability Transition Pore; D009336:Necrosis / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000502:physiology
chemical_list: D065095:Calcineurin Inhibitors; D005452:Fluoresceins; D005456:Fluorescent Dyes; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D015800:Protozoan Proteins; D017382:Reactive Oxygen Species; C085925:calcein AM; D016572:Cyclosporine; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D021983:Cyclophilins
keywords: Trypanosoma cruzi; cyclophilin; cyclosporin A; oxidative stress; programmed cell death