TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human bloodReportar como inadecuado




TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

1 Biologie Intégrée du Globule Rouge 2 LBI2M - Laboratoire de Biologie Intégrative des Modèles Marins 3 LIT - Laboratoire d-Innovation Thérapeutique 4 LBM - Laboratoire des biomolécules

Abstract : After invading red blood cells RBCs, Plasmodium falciparum Pf can export its own proteins to the host membrane and activate endogenous channels that are present in the membrane of RBCs. This transport pathway involves the Voltage Dependent Anion Channel VDAC. Moreover, ligands of the VDAC partner TranSlocator PrOtein TSPO were demonstrated to inhibit the growth of the parasite. We studied the expression of TSPO and VDAC isoforms in late erythroid precursors, examined the presence of these proteins in membranes of non-infected and infected human RBCs, and evaluated the efficiency of TSPO ligands in inhibiting plasmodium growth, transporting the haem analogue Zn-protoporphyrin-IX ZnPPIX and enhancing the accumulation of reactive oxygen species ROS. TSPO and VDAC isoforms are differentially expressed on erythroid cells in late differentiation states. TSPO2 and VDAC are present in the membranes of mature RBCs in a unique protein complex that changes the affinity of TSPO ligands after Pf infection. TSPO ligands dose-dependently inhibited parasite growth, and this inhibition was correlated to ZnPPIX uptake and ROS accumulation in the infected RBCs. Our results demonstrate that TSPO ligands can induce Pf death by increasing the uptake of porphyrins through a TSPO2–VDAC complex, which leads to an accumulation of ROS.





Autor: I Marginedas-Freixa - C Hattab - G Bouyer - F Halle - A Chene - S.D. Lefevre - M Cambot - A Cueff - M Schmitt - B Gamain - Jean-J

Fuente: https://hal.archives-ouvertes.fr/



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