We have studied the action of diphtheria toxin, modeccin and ricin on HeLa cells infected by Trypanosoma cruzi. Parasitized HeLa cells were resistant to diphtheria toxin and modeccin, whereas non-parasitized cells from the same cultures and control cultures showed cytopathological alterations. Protein synthesis, assayed by the incorporation of labelled methionine, diminished in toxin-treated control cultures but remained unaltered in the infected ones, compared to synthesis by untreated infected cells. Ricin, on the other hand, is a toxin that enters the cytoplasm by endocytosis. It has greater cytopathological effects in parasitized cells than in non-parasitized ones from the same cultures or uninfected control cells. Protein synthesis was inhibited in infected cultures treated with ricin.
The lack of definitive chemotherapeutic agents to fight against visceral leishmaniasis has lead to the testing of numerous compounds. In the present work, we carry out an in-depth study of the activity against Leishmania donovani of three acridine derivatives both in vitro and in vivo. These compounds have proven to be highly effective at medium and high concentrations of 10 µg/ml, against both flagellate and nonflagellate forms of the parasite, which, though obtained in vitro, closely resemble natural intracellular amastigotes. The in vivo assays showed a significant reduction in the percentage of parasitation versus control, for all the compounds tested. In addition, we have studied the possible mechanism by which these acridine derivatives act: they displayed a greater inhibitory effect against macromolecule synthesis in treated flagellates, yet alterations are also caused in the production of end metabolites and in the activity of different enzymes. The data obtained indicate that the acridine derivatives had several targets, one of them is the synthesis of nucleic acids and proteins, while the second one might be interaction with the carbohydrate and energy-production processes in the parasite. This conclusion is consistent with our observations concerning the ultrastructural changes induced in the parasite by these compounds principally at the mitochondrial level.
The present study of the synthesis of new proteins in plant trypanosomatids in the genus Phytomonas as a response to different types of stress demonstrates the production of a number of proteins that can be grouped into four families similar to those that appear in other organisms (heat-shock proteins). In the study of stress, Phytomonas cultures were subjected to changes in temperature from 22 degrees to 37 degrees C, deprived of glucose, grown in the presence of sodium arsenite, and treated with calcium ionophore. In addition, the culture medium was changed from Grace's medium (330 mosmol/1) to a plant-culture medium with an osmolarity of 286 mosmol/l, implying the exertion of stress during the parasite's normal biological cycle of passage from the insect vector to the plant host. The treatment with actinomycin D demonstrated that some of the mRNAs that codify these proteins are found in normal presynthesized conditions. To measure the effect of temperature on the macromolecule biosynthesis we compared the incorporation of labeled analogues ([3H]-thymidine, [3H]-uridine, and [3H]-leucine) by flagellates cultured at 22 degrees C with that by parasites cultivated at 37 degrees C.
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