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Mol Biochem Parasitol
2009 Nov 01;1681:113-6. doi: 10.1016/j.molbiopara.2009.06.008.
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Comparison of effects of green tea catechins on apicomplexan hexose transporters and mammalian orthologues.
Slavic K
,
Derbyshire ET
,
Naftalin RJ
,
Krishna S
,
Staines HM
.
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Here we have investigated the inhibitory properties of green tea catechins on the Plasmodium falciparum hexose transporter (PfHT), the Babesia bovis hexose transporter 1 (BboHT1) and the mammalian facilitative glucose transporters, GLUT1 and GLUT5, expressed in Xenopus laevis oocytes. (-)-Epicatechin-gallate (ECG) and (-)-epigallocatechin-gallate (EGCG) inhibited D-glucose transport by GLUT1 and PfHT, and D-fructose transport by GLUT5, with apparent K(i) values between 45 and 117 microM. BboHT1 was more potently inhibited by the ungallated catechins (-)-epicatechin (EC) and (-)-epigallocatechin (EGC), with apparent K(i) values of 108 and 168 microM, respectively. Site-directed mutagenesis experiments provided little further support for previously reported models of catechin binding to hexose transporters. Furthermore, P. falciparum growth inhibition by catechins was not affected by the external D-glucose concentration. Our results provide new data on the inhibitory action of catechins against sugar transporters but were unable to elucidate the antimalarial mechanism of action of these agents.
Fig. 1. Sequence alignments of helix VIII from apicomplexan and mammalian hexose transporters and effect of catechins (0.5 mM) on hexose transport by wild-type (closed bars) and mutant hexose transporters (open bars). (A) The Clustal W program was used to generate the alignment. Bold residues were substituted in site-directed mutagenesis experiments. Note: NT are putative anchoring residues of GLUT1 with gallated catechins [8]. GLUT2, mammalian facilitated glucose transporter 2; GLUT4, mammalian facilitated glucose transporter 4; PvHT, Plasmodium vivax hexose transporter; PkHT, P. knowlesi hexose transporter; PyHT, P. yoelii hexose transporter, TgGT1, Toxoplasma gondii glucose transporter 1; THT1, T. brucei hexose transporter 1. (B) Wild-type PfHT versus N341L PfHT, (C) wild-type GLUT1 versus N317L GLUT1 and (D) wild-type BboHT1 versus L323N BboHT1. Uptake of [14C] d-glucose by PfHT, GLUT1 and BboHT1 was measured. All values were first corrected for the uptake into water-injected controls and are presented as a percentage of paired control experiments performed in the absence of any inhibitor. Data are averaged from three experiments, each on oocytes from a different toad, and are shown as means ± SEM. *Significantly different from wild-type (P < 0.001).
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