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Determination of glutathione redox potential and pH value in subcellular compartments of malaria parasites.

Identifieur interne : 000376 ( Main/Exploration ); précédent : 000375; suivant : 000377

Determination of glutathione redox potential and pH value in subcellular compartments of malaria parasites.

Auteurs : Franziska Mohring [Allemagne] ; Mahsa Rahbari [Allemagne] ; Bernd Zechmann [États-Unis] ; Stefan Rahlfs [Allemagne] ; Jude M. Przyborski [Allemagne] ; Andreas J. Meyer [Allemagne] ; Katja Becker [Allemagne]

Source :

RBID : pubmed:28062360

Descripteurs français

English descriptors

Abstract

The malaria parasite Plasmodium falciparum is exposed to multiple sources of oxidative challenge during its complex life cycle in the Anopheles vector and its human host. In order to further elucidate redox-based parasite host cell interactions and mechanisms of drug action, we targeted the genetically encoded glutathione redox sensor roGFP2 coupled to human glutaredoxin 1 (roGFP2-hGrx1) as well as the ratiometric pH sensor pHluorin to the apicoplast and the mitochondrion of P. falciparum. Using live cell imaging, this allowed for the first time the determination of the pH values of the apicoplast (7.12±0.40) and mitochondrion (7.37±0.09) in the intraerythrocytic asexual stages of the parasite. Based on the roGFP2-hGrx1 signals, glutathione-dependent redox potentials of -267mV and -328mV, respectively, were obtained. Employing these novel tools, initial studies on the effects of redox-active agents and clinically employed antimalarial drugs were carried out on both organelles.

DOI: 10.1016/j.freeradbiomed.2017.01.001
PubMed: 28062360


Affiliations:


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Le document en format XML

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<term>Animals (MeSH)</term>
<term>Anopheles (parasitology)</term>
<term>Antimalarials (metabolism)</term>
<term>Antimalarials (therapeutic use)</term>
<term>Apicoplasts (metabolism)</term>
<term>Glutaredoxins (genetics)</term>
<term>Glutaredoxins (metabolism)</term>
<term>Glutathione (genetics)</term>
<term>Glutathione (metabolism)</term>
<term>Green Fluorescent Proteins (metabolism)</term>
<term>Host-Parasite Interactions (genetics)</term>
<term>Humans (MeSH)</term>
<term>Hydrogen-Ion Concentration (MeSH)</term>
<term>Malaria, Falciparum (drug therapy)</term>
<term>Malaria, Falciparum (metabolism)</term>
<term>Malaria, Falciparum (parasitology)</term>
<term>Mitochondria (metabolism)</term>
<term>Oxidation-Reduction (MeSH)</term>
<term>Oxidative Stress (genetics)</term>
<term>Plasmodium falciparum (genetics)</term>
<term>Plasmodium falciparum (metabolism)</term>
<term>Plasmodium falciparum (pathogenicity)</term>
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<term>Animaux (MeSH)</term>
<term>Anopheles (parasitologie)</term>
<term>Antipaludiques (métabolisme)</term>
<term>Antipaludiques (usage thérapeutique)</term>
<term>Apicoplastes (métabolisme)</term>
<term>Concentration en ions d'hydrogène (MeSH)</term>
<term>Glutarédoxines (génétique)</term>
<term>Glutarédoxines (métabolisme)</term>
<term>Glutathion (génétique)</term>
<term>Glutathion (métabolisme)</term>
<term>Humains (MeSH)</term>
<term>Interactions hôte-parasite (génétique)</term>
<term>Mitochondries (métabolisme)</term>
<term>Oxydoréduction (MeSH)</term>
<term>Paludisme à Plasmodium falciparum (métabolisme)</term>
<term>Paludisme à Plasmodium falciparum (parasitologie)</term>
<term>Paludisme à Plasmodium falciparum (traitement médicamenteux)</term>
<term>Plasmodium falciparum (génétique)</term>
<term>Plasmodium falciparum (métabolisme)</term>
<term>Plasmodium falciparum (pathogénicité)</term>
<term>Protéines à fluorescence verte (métabolisme)</term>
<term>Stress oxydatif (génétique)</term>
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<term>Glutaredoxins</term>
<term>Glutathione</term>
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<term>Antimalarials</term>
<term>Glutaredoxins</term>
<term>Glutathione</term>
<term>Green Fluorescent Proteins</term>
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<term>Malaria, Falciparum</term>
</keywords>
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<term>Host-Parasite Interactions</term>
<term>Oxidative Stress</term>
<term>Plasmodium falciparum</term>
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<term>Glutarédoxines</term>
<term>Glutathion</term>
<term>Interactions hôte-parasite</term>
<term>Plasmodium falciparum</term>
<term>Stress oxydatif</term>
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<term>Apicoplasts</term>
<term>Malaria, Falciparum</term>
<term>Mitochondria</term>
<term>Plasmodium falciparum</term>
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<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Antipaludiques</term>
<term>Apicoplastes</term>
<term>Glutarédoxines</term>
<term>Glutathion</term>
<term>Mitochondries</term>
<term>Paludisme à Plasmodium falciparum</term>
<term>Plasmodium falciparum</term>
<term>Protéines à fluorescence verte</term>
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<term>Paludisme à Plasmodium falciparum</term>
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<term>Malaria, Falciparum</term>
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<term>Plasmodium falciparum</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr">
<term>Plasmodium falciparum</term>
</keywords>
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<term>Hydrogen-Ion Concentration</term>
<term>Oxidation-Reduction</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
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<term>Concentration en ions d'hydrogène</term>
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<div type="abstract" xml:lang="en">The malaria parasite Plasmodium falciparum is exposed to multiple sources of oxidative challenge during its complex life cycle in the Anopheles vector and its human host. In order to further elucidate redox-based parasite host cell interactions and mechanisms of drug action, we targeted the genetically encoded glutathione redox sensor roGFP2 coupled to human glutaredoxin 1 (roGFP2-hGrx1) as well as the ratiometric pH sensor pHluorin to the apicoplast and the mitochondrion of P. falciparum. Using live cell imaging, this allowed for the first time the determination of the pH values of the apicoplast (7.12±0.40) and mitochondrion (7.37±0.09) in the intraerythrocytic asexual stages of the parasite. Based on the roGFP2-hGrx1 signals, glutathione-dependent redox potentials of -267mV and -328mV, respectively, were obtained. Employing these novel tools, initial studies on the effects of redox-active agents and clinically employed antimalarial drugs were carried out on both organelles.</div>
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