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.
D000818:Animals; D000518:Eflornithine / Q000494:pharmacology*; D007930:Leucine / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis; D019814:Myristic Acid; D009227:Myristic Acids / Q000378:metabolism; D014176:Protein Biosynthesis; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000378:metabolism*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000096:biosynthesis
D008565:Membrane Proteins; D009227:Myristic Acids; D014643:Variant Surface Glycoproteins, Trypanosoma; D019814:Myristic Acid; D007930:Leucine; D000518:Eflornithine