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Effects of microtubule inhibitors on protein synthesis inPlasmodium falciparum

Abstract

At low concentrations, both isomers of tubulozole (C, T) inhibitPlasmodium falciparum but only tubulozole C inhibits mammalian cells. Since tubulozole C prevents polymerization of mammalian tubulin whereas tubulozole T does not, the antimalarial action of tubulozoles may not involve microtubules. The present study concerns the inhibition of parasite protein synthesis by the tubulozoles. While tubulozoles took 3–4 h to kill parasites in erythrocytic culture, they inhibited protein synthesis within 10 min. The concentrations of the drug required were, however, too high for this to account for their antimalarial action. The microtubule inhibitor colcemid inhibited protein synthesis rapidly and at relevant concentrations, but vinblastine did not inhibit protein synthesis. Tubulozole T and colcemid inhibited protein synthesis posttranscriptionally since they had little effect on RNA synthesis. Analysis of labelled parasite proteins by two-dimensional gel electrophoresis showed that while it inhibited synthesis of most proteins to the same degree, tubulozole T super-inhibited the synthesis of certain proteins. This may cause its antimalarial effect at low concentrations.

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Abbreviations

DMSO:

dimethylsulphoxide

SDS:

sodium dodecyl sulphate

IC50 :

drug concentration inhibiting parasite growth or protein synthesis by 50%

TCA:

trichloroacetic acid

HEPES:

N-2-hydroxyethylpiperazine-N-2-ethanesulphonic acid

MW:

molecular weight

pI:

isoelectric point

hsp:

heat shock protein

grp:

glucose-regulated protein

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Correspondence to A. Bell.

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Bell, A., Wernli, B. & Franklin, R.M. Effects of microtubule inhibitors on protein synthesis inPlasmodium falciparum . Parasitol Res 79, 146–152 (1993). https://doi.org/10.1007/BF00932261

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Keywords

  • Protein Synthesis
  • Mammalian Cell
  • Vinblastine
  • Relevant Concentration
  • Inhibit Protein Synthesis