Effects of alpha-difluoromethylornithine on protein synthesis and synthesis of the variant-specific glycoprotein (VSG) in Trypanosoma brucei brucei.

Protein synthesis in Trypanosoma brucei brucei was rapidly inhibited during polyamine depletion by DL-alpha-difluoromethylornithine (DFMO) in vitro and in vivo. [3H]Leucine incorporation was depressed 30-40% by 24 h and 80-90% by 48 h of DFMO treatment. Concomitantly there was an apparent decrease in the synthesis of the variant-specific glycoprotein (VSG) in DFMO-treated trypanosomes, as measured by decreased incorporation of [3H]myristic acid into VSG. The discovery of decreased protein synthesis in T. b. brucei during DFMO treatment is noteworthy, because it was reported previously that protein synthesis was paradoxically stimulated 2-4-fold during DFMO treatment in these organisms. Decreased protein synthesis probably relates to the biochemical mechanism of action of DFMO on trypanosomes.