Leishmania donovani mitochondrial iron superoxide dismutase A is released into the cytosol during miltefosine induced programmed cell death.
Mol Biochem Parasitol
; 183(1): 42-51, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22342963
ABSTRACT
The oxidative phosphorylation process is the main source of endogenous reactive oxygen species (ROS) such as superoxide in mitochondria. In mammals, manganese superoxide dismutase plays an important role in detoxification of superoxide before it interferes with mitochondrial function and causes programmed cell death. Here, we investigated the role of Leishmania donovani mitochondrial iron superoxide dismutase-A (LdFeSODA) in protecting the parasite from oxidative stress and in the control of programmed cell death events. We have shown that overexpression of LdFeSODA protects Leishmania donovani from miltefosine induced cytotoxicity and reduced mitochondrial-derived superoxide generation. Furthermore, parasites overexpressing LdFeSODA showed (i) lower level of phosphatidylserine exposure as measured by flow cytometry and fluorescent microscopy; and (ii) reduced level of TUNEL staining of parasites compared to the control parasites. Finally, prolonged incubation of the parasites with miltefosine induced the release of both cytochrome C and LdFeSODA into the cytosol as demonstrated by Western blotting and fluorescence microscopy indicating programmed cell death. The results indicate that LdFeSODA protects the mitochondria of Leishmania from oxidative stress thereby inhibiting programmed cell death.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosforilcolina
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Superóxido Dismutase
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Leishmania donovani
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Proteínas de Protozoários
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Apoptose
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Citosol
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Proteínas Mitocondriais
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Antiprotozoários
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Canadá