Differential toxicity of ricin and diphtheria toxin for bloodstream forms of Trypanosoma brucei.
The cytotoxicity of ricin and diphtheria toxin was studied in culture-adapted bloodstream forms of Trypanosoma brucei. Although ricin is endocytosed at a rate comparable to that of other internalized macromolecules, it is nontoxic to bloodstream-form trypanosomes. The resistance lies partly in low susceptibility of the targeted ribosomes: T. brucei cell-free protein biosynthesis is only partially inhibited by ricin A chain. In addition, ricin is degraded before it reaches the ribosomes, as the toxin is delivered to lysosomes. In contrast, diphtheria toxin shows similar cytotoxicities for bloodstream-form trypanosomes and mouse myeloma cells. Both trypanosome and myeloma cells are more than 1000-fold less sensitive to the action of the toxin than most other mammalian cell lines, although nicked reduced diphtheria toxin inhibits cell-free protein synthesis of T. brucei and myeloma cells to the same extent as that of a rabbit reticulocyte lysate. The effect of diphtheria toxin on T. brucei in vitro translation is NAD+ dependent, suggesting that ADP-ribosylation of elongation factor 2 could be the cause of the inhibition as it is in mammalian cells. Thus, the toxic moiety of diphtheria toxin is suitable for preparation of cell-type-specific cytotoxic reagents directed towards trypanosomes.
Scory
S
S
Abteilung Parasitologie, Hygiene-Institut der Ruprecht-Karls-Universität, Heidelberg, Germany.
Steverding
D
D
D000818:Animals; D002474:Cell-Free System; D004167:Diphtheria Toxin / Q000378:metabolism / Q000633:toxicity*; D004705:Endocytosis; D051379:Mice; D011480:Protease Inhibitors / Q000494:pharmacology; D014176:Protein Biosynthesis; D015800:Protozoan Proteins / Q000096:biosynthesis; D011817:Rabbits; D012276:Ricin / Q000378:metabolism / Q000633:toxicity*; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004167:Diphtheria Toxin; D011480:Protease Inhibitors; D015800:Protozoan Proteins; D012276:Ricin