Analysis of P-glycoprotein expression in purified parasite plasma membrane and food vacuole from Plasmodium falciparum.
A P-glycoprotein homologue (Pgh1) is believed to play a role in modulating levels of chloroquine resistance in Plasmodium falciparum. To study the role of Pgh1 in the mechanism of chloroquine (CQ) resistance, antisera were raised against this protein. There was no direct association between the level of Pgh1 expression and chloroquine sensitivity. We also failed to detect phosphorylation of Pgh1 in the food vacuole (FV), suggesting that other mechanisms regulate the chloroquine-resistant (CQR) phenotype. Therefore, high levels of expression of Pgh1 or phosphorylation of this protein in the FV could not account for CQ sensitivity. In addition, the lack of inhibition of CQ accumulation by anti-Pgh1 antibodies suggests that Pgh1 is not involved as a CQ transporter in the plasma membrane of P. falciparum. Furthermore, resistance reversers do not appear to act at the plasma membrane level.
Elandaloussi
Laurence M
LM
Department of Pharmacology, University of Cape Town, Observatory 7925, Cape Town, South Africa. laurence.elandaloussi@irta.es
Lindt
Meinrad
M
Collins
Malcolm
M
Smith
Peter J
PJ
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002738:Chloroquine / Q000378:metabolism / Q000494:pharmacology*; D004351:Drug Resistance; D007106:Immune Sera / Q000378:metabolism; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D014617:Vacuoles / Q000737:chemistry*
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D007106:Immune Sera; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine