Differential toxicity of ricin and diphtheria toxin for bloodstream forms of Trypanosoma brucei

Scory, Stefan; Steverding, Dietmar

doi:10.1016/s0166-6851(97)00162-x

Cited by 7 publications

(8 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1) were determined in vitro by a growth inhibition assay previously described for bloodstream forms of T. brucei (Scory and Steverding 1997). NP-L 3 MeVS and its iodine derivative NIP-L 3 MeVS, as well as AdaYAhx 3 -L 3 MeVS, exhibited only weak antitrypanosomal activities with 50% effective dose (ED 50 ) values in the mid-micromolar to low-micromolar range (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Trypanocidal activities of trileucine methyl vinyl sulfone proteasome inhibitors

et al. 2004

Self Cite

View full text Add to dashboard Cite

Previous studies have shown that proteasome inhibitors are novel agents for chemotherapy of human African trypanosomiasis or sleeping sickness. In this study, five peptide trileucine methyl vinyl sulfones with different N-terminal substituents were tested for their trypanocidal activities in vitro using culture-adapted bloodstream forms of Trypanosoma brucei. Two inhibitors displayed promising anti-trypanosomal activities with ED50 values in the sub-micromolar range. Higher trypanocidal activity of the compounds generally corresponded to a higher k(obs)/[I] value for inhibition of the trypsin-like activity but not for the inhibition of the chymotrypsin-like activity of the proteasome. These data suggest that inhibitors with strong activity against the trypsin-like activity of the proteasome are the rational choice for future anti-sleeping sickness drug development.

show abstract

Section: Resultsmentioning

confidence: 99%

Trypanocidal activities of trileucine methyl vinyl sulfone proteasome inhibitors

et al. 2004

Self Cite

View full text Add to dashboard Cite

show abstract

“…For more details about the composition of the essential oils see elsewhere (6). To screen essential oils and isolated mono-and sesquiterpenes for their antitrypanosomal and antileishmanial activity, an in vitro growth inhibition assay with bloodstream forms of T. brucei (8) and promastigotes of L. major (9) was used. The cytotoxicity of the test compounds was colorimetrically determined with the oxidation-reduction indicator Alamar Blue (10).…”

mentioning

confidence: 99%

In vitro Effect of Essential Oils and Isolated Mono- and Sesquiterpenes on Leishmania major and Trypanosoma brucei

Mikus¹,

Harkenthal²,

Steverding³

et al. 2000

Planta Med

Self Cite

134

View full text Add to dashboard Cite

The effect of different essential oils as well as of isolated mono- and sesquiterpenes on the viability of bloodstream forms of Trypanosoma brucei, promastigotes of Leishmania major and human HL-60 cells was evaluated using the Almar Blue assay. Of the 12 essential oils and 8 terpenes investigated, only three essential oils, Melissa officinalis (balmmint) oil, Thymus vulgaris (thyme) oil, and Melaleuca alternifolia (tea tree) oil were about 50-fold and 80-fold more toxic to bloodstream forms of T. brucei than to HL-60 cells, respectively. Terpinen-4-ol, the main compound of the Australian tea tree oil, was even 1000-fold more toxic to trypanosomes than to the human cells. On the other hand, none of the essential oils and terpenes tested were more toxic to promastigotes of L. major than to HL-60 cells.

show abstract

“…On the other hand, trypanosomatid ribosomes have been shown to be highly resistant, in comparison to mammalian particles, to two ribosome inactivating proteins; ricin and trichosanthin [70,71]. These toxins bind initially to the ribosomal stalk and depurinate a conserved base on the 28S rRNA, blocking the binding of EF-2 to ribosomes, supporting the idea that the trypanosomatid stalk has specific features.…”

Section: Elongation Factorsmentioning

confidence: 98%

“…I n c o n t r a s t t o S c E F -2 t h a t i s r e g u l a t e d b y phosphorylation of Threonine 57, TcEF-2 presented a Methionine in this position, suggesting a lack of regulation through phosphorylation (Figure 11). The histidine involved in ADP-ribosylation in ScEF-2 (H699) is conserved in trypanosomatids (H703 in T. cruzi), and consequently, diphtheria toxin inactivates protein synthesis in T. brucei [70]. Secondary structure comparative analysis showed an overall conserved architecture.…”

Section: Elongation Factorsmentioning

confidence: 99%

Ribosomes from Trypanosomatids: Unique Structural and Functional Properties

Ayub¹,

Lapadula²,

Hoebeke³

et al. 2012

Cell-Free Protein Synthesis

View full text Add to dashboard Cite

Additional information is available at the end of the chapter http://dx.doi.org/10.5772/48336 IntroductionTrypanosomatids are a monophyletic group of protozoa that diverged early from the eukaryotic lineage, constituting valuable model organisms for studying variability in different highly conserved processes including protein synthesis. Moreover, several species of trypanosomatids are causing agents of endemic diseases in the third world. There are many evidences suggesting that translation in these organisms shows important differences with that of model organisms such as yeast and mammals. These unique features, which have a great potential relevance for both basic and applied research, will be discussed in this chapter. Structural analysis Cryo-electron microscopy map of Trypanosoma cruzi ribosome: Unique features of the rRNAUsing the cryo-electron microscopy (cryo-EM) technique, a 12Å resolution density map of the T. cruzi 80S ribosome has been constructed [1]. The overall structure of the T. cruzi 80S ribosome exhibits well defined small (40S) and large (60S) subunits (Figure 1). Some of the landmark characteristics of the ribosome structure can be identified in the density map. Compared with the 80S ribosome from yeast, both the small and large ribosomal subunits from T. cruzi are larger, mainly due to the size of the ribosomal RNA molecules. T. cruzi rRNA (18S rRNA: 2,315 nt and 28S rRNA: 4,151 nt) is one-fifth larger than yeast rRNA (18S rRNA: 1,798 nt; 25S rRNA: 3,392 nt) in total number of nucleotides.Although the T. cruzi 80S ribosome possesses conserved ribosomal structures, it exhibits many distinctive structural features in both the small and large subunits. Compared with other eukaryotic ribosomes, the T. cruzi ribosomal 40S subunit appears expanded, due to the addition of a large piece of density adjacent to the platform region ( Figure 1). As can be seen in the secondary structure of the T. cruzi 18S rRNA (Figure 2), this extra density must be attributed to two large expansion segments (ES) in domain II of the 18S rRNA, ES6 and ES7, designated as insertions of helices 21 and 26. These are the two largest ES in the T. cruzi 18S rRNA, involving 504 and 147 nucleotides, respectively.

show abstract

Differential toxicity of ricin and diphtheria toxin for bloodstream forms of Trypanosoma brucei

Cited by 7 publications

References 30 publications

Trypanocidal activities of trileucine methyl vinyl sulfone proteasome inhibitors

Trypanocidal activities of trileucine methyl vinyl sulfone proteasome inhibitors

In vitro Effect of Essential Oils and Isolated Mono- and Sesquiterpenes on Leishmania major and Trypanosoma brucei

Ribosomes from Trypanosomatids: Unique Structural and Functional Properties

Contact Info

Product

Resources

About