Der humane Transporter EAAT 3 ist ein Kandidat für die Vermittlung der L-Glutamat-Aufnahme in Plasmodium falciparum-infizierte Erythrozyten

Der obligat intrazelluläre Parasit Plasmodium falciparum, der Erreger der Malaria tropica, vollzieht einen Teil seiner Entwicklung in humanen Erythrozyten. Aus immunologischer Sicht stellt der Erythrozyt als Wirtszelle eine sichere Umgebung dar. Er erweist sich jedoch für die Nährstoffversorgung des...

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Bibliographic Details
Main Author: Winterberg, Markus
Contributors: Lingelbach, Klaus (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2009
Online Access:PDF Full Text
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The intracellular parasite Plasmodium falciparum, the causative agent of Malaria tropica, invades human erythrocytes. After invasion the parasite is largely hidden from immune recognition but confronted with a limited nutrition supply. Therefore the parasite induces an increase in solute transport across the host plasma membrane, the so-called novel permeation pathways (NPP). These alterations in the permeability of the erythrocyte plasma membrane assure the supply of nutrients and the disposal of waste products. This study investigates the mechanisms involved in transport of amino acids across the plasma membrane of infected human erythrocytes. In this context it was shown that treatment with sodium arsenite induces NPP-like permeability in non-infected erythrocytes. The induced permeability is limited to negatively charged amino acids and shows characteristics of an EAAT-mediated transport. The influx of glutamate and aspartate into the arsenite-treated erythrocytes is sodium dependent, stereoselective for L-glutamate and sensitive to known EAAT-specific Inhibitors like cis-ACBD and HIP-A. These properties can also be found in Plasmodium-infected cells, suggesting that an EAAT-type transporter is involved in formation of the NPP. Moreover this study provides evidence that the NPP comprise at least three independent pathways for amino acids.