ترجمه مقاله جابجایی و انتقال گلوکز در پروماستیگوت و آماستیگوت لیشمانیا Mexicana - نشریه الزویر

Promastigotes and amastigotes of Luishmania mexicana mexicana transported 2-deoxy-D-glucose (2-DOG) by a saturable process with a K,,, of 24 f 3 PM and V,, of 2.21 nmol min-’ (mg protein)-’ for the promastigote and a K,,,of29&8pMand V_ of 0.13 nmol min-’ (mg protein)-’ for the amastigote stage. Amastigotes incorporated 2- DOG maximally at pH 5.0, while for promastigotes the optimum was at pH 7.0. Mid-log phase promastigotes were found to accumulate 2-DOG via a stereospecific carrier-mediated process which was competitively inhibited by Dglucose and Dmannose but not L-glucose. Transport was dependent upon temperature, with a QIO in promastigotes of 1.83 and an optimum rate at 35°C (*4”C) with an activation energy of 50.12 kJ mol-‘. Stationary phase promastigotes accumulated 2-DOG at approximately twice the rate of mid-log phase promastigotes. Cytochalasin B, forskolin and phloretin were all found to inhibit human erythrocyte 2-DOG uptake but only cytochalasin B was found significantly to inhibit promastigote 2-DOG uptake. Interestingly, leishmanial2-DOG uptake was inhibited by a series of membrane potential antagonists including the ionophore monensin, the H’ATPase inhibitor N,N’- dicyclohexylcarbodiimide (DCCD) and uncoupling agent carbonylcyanide+(triflouromethoxy) phenylhydrazone (FCCP), as well as, the tricyclic drugs chlomipramine and imipramine, but was insensitive to the Na+/K+ATPase inhibitor ouabain and the antitrypanosomal drugs Pentostam and Suramin. We therefore conclude that there are significant structural and mechanistic differences between the D-glucose uptake systems of Leishmania and the mammalian host to merit the inclusion of glucose transporters as putative targets for rational drug design.