Molecular identification and functional analysis of Plasmodium vivax hexose transporter 1 NorthKorean (PvHT1NK) type

초록

Plasmodium vivax is the most widely distributed human malaria parasites. Because the appearance of drug-resistant Plasmodium species, novel mechanisms of action are needed. The glucose uptake blocking strategy was suggested for novel mode of action that leads to selective starvation of parasites. The PvHT1NK was isolated using RT-PCR from patient blood. The 191-195and 381-387 amino acids are different from that of Salvador I PvHT. PvHT1NK expressed Xenopus laevis oocytes mediated the transport of [3H]deoxy-D-glucose (dDG) in an expression and incubation time-dependent manner without sodium dependency. PvHT1 showed no exchange mode of glucose in efflux experiments and dose-dependent results showed saturable kinetics. The Eadie-Hofstee analysis revealed a Km value of 294.1 μM and a Vmax value of 1,060 pmol/oocyte/hr. From the inhibition experiments showed that the IC50 values of dDG, glucose, mannose, and Methyl-DG were 1.20 ± 0.19 mM, 0.26 ± 0.01 mM, 0.25 ± 0.02 mM, and 0.40± 0.06 mM, respectively. These results provide properties of glucose uptake via PvHT1NK for carbohydrate metabolism and support approaches to vivax malaria drug development strategy for starving of parasite