Comparison of effects of green tea catechins on apicomplexan hexose transporters and mammalian orthologues

Ksenija Slavic,Elvira T Derbyshire,Richard J Naftalin,Sanjeev Krishna,Henry M Staines

doi:10.1016/j.molbiopara.2009.06.008

Abstract

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 Ki values between 45 and 117μM. BboHT1 was more potently inhibited by the ungallated catechins (−)-epicatechin (EC) and (−)-epigallocatechin (EGC), with apparent Ki values of 108 and 168μM, 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.

Highlights

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, glucose transporter 1 (GLUT1) and GLUT5, expressed in Xenopus laevis oocytes. (−)-Epicatechin-gallate (ECG) and (−)-epigallocatechin-gallate (EGCG) inhibited d-glucose transport by GLUT1 and PfHT, and dfructose transport by GLUT5, with apparent Ki values between 45 and 117 ␮M
These findings may be relevant to the P. falciparum hexose transporter, PfHT, a parasite plasma membranelocalised protein that is the major route for parasite d-glucose and d-fructose uptake [9,10]
The effect of the green tea catechins, EC, ECG, EGC and EGCG, on d-glucose transport via PfHT, GLUT1 and the Babesia bovis hexose transporter 1 (BboHT1; [12]) and d-fructose transport via GLUT5 was assayed in Xenopus laevis oocytes expressing each of the hexose transporters, using methods described previously [12]

Summary

Introduction

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 dfructose transport by GLUT5, with apparent Ki values between 45 and 117 ␮M. (−)-Epicatechin-gallate (ECG) and (−)-epigallocatechin-gallate (EGCG) inhibited d-glucose transport by GLUT1 and PfHT, and dfructose transport by GLUT5, with apparent Ki values between 45 and 117 ␮M.

Results

Conclusion