Differential regulation of putrescine uptake in trypanosoma cruzi and other trypanosomatids

González, Nélida S.; Ceriani, Carolina; Algranati, Israel D.

doi:10.1016/0006-291x(92)92358-5

Cited by 30 publications

(25 citation statements)

References 14 publications

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“…Its uptake is stageand cell cycle-regulated (Gonzalez et al, 1992), suggesting its importance in cell growth and differentiation. Interestingly, although not essential, addition of putrescine to ODC-deficient L. donovani mutants restores parasite growth more rapidly and to a greater extent than PAs such as spermidine (Jiang et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis

et al. 2008

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Polyamines are important regulators of growth and differentiation in a variety of cells, including parasitic protozoa. Promastigotes of Leishmania species have high levels of putrescine and spermidine and their growth can be inhibited by polyamine biosynthesis antagonists. The putrescine analogue 1,4-diamino-2-butanone (DAB) is microbicidal against Tritrichomonas foetus and Trypanosoma cruzi, so we tested its effects on Leishmania amazonensis proliferation, viability, organization, putrescine transport and synthesis as well as in vitro infectivity. DAB impaired promastigote proliferation dose-dependently (IC 50 144 mM) and the parasite putrescine concentration was reduced by nearly 50 %. This analogue markedly inhibited both ornithine decarboxylase activity and [H 3 ]putrescine uptake by promastigotes. Pre-treatment with DAB for 24 h led to compensatory enhancement of putrescine uptake, indicating an adaptive mechanism in DAB-treated parasites. Remarkably, DAB caused mitochondrial damage, assessed by transmission electron microscopy, and 3 h treatment with 1 mM DAB enhanced lipid peroxidation, whereas incubation with 10 mM DAB or for 24 h resulted in decreased peroxidation levels in the parasites. This effect was probably due to the loss of mitochondrial function, demonstrated by the diminished reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), not observed in macrophages. Murine macrophages infected with L. amazonensis amastigotes treated with DAB had parasite loads significantly (P,0.05) lower than controls, presumably due to interference with putrescine uptake and/or synthesis. These results suggest that putrescine may be involved in leishmanial survival, possibly by maintaining the parasite's mitochondrial function. The use of analogues to interfere with polyamine/diamine synthesis and transport may shed light on its function in intracellular parasite survival and lead to identification of new targets for leishmaniasis chemotherapy.

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Section: Discussionmentioning

confidence: 99%

The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis

et al. 2008

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“…The lack of de novo putrescine synthesis in T. cruzi seems to be compensated by the presence of a constitutive and active transport system specific for putrescine which cannot be stimulated by DFMO and allows the uptake of putrescine from the external medium [8,16,17]. In contrast, other trypanosomatid protozoa such as Crithidia fitsciculata and Leishmania mexicana have shown an inducible putrescine transport system.…”

Section: Introductionmentioning

confidence: 98%

“…In contrast, other trypanosomatid protozoa such as Crithidia fitsciculata and Leishmania mexicana have shown an inducible putrescine transport system. In the latter cases the uptake of putrescine is markedly enhanced after the depletion of intracellular polyamines [8,16,18].…”

Section: Introductionmentioning

confidence: 99%

Trypanosoma cruzi epimastigotes lack ornithine decarboxylase but can express a foreign gene encoding this enzyme

et al. 1999

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“…As a unicellular eukaryote with a high replication rate, T. cruzi depends on polyamine production and͞or uptake from the extracellular medium for propagation (16). Previous studies failed to detect ornithine decarboxylase activity in T. cruzi.…”

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confidence: 99%

l -Arginine-dependent suppression of apoptosis in Trypanosoma cruzi : Contribution of the nitric oxide and polyamine pathways

Piacenza

Peluffo

Radí

2001

Proc. Natl. Acad. Sci. U.S.A.

114

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Until recently, a capacity for apoptosis and synthesis of nitric oxide ( ⅐ NO) were viewed as exclusive to multicellular organisms. The existence of these processes in unicellular parasites was recently described, with their biological significance remaining to be elucidated. We have evaluated L-arginine metabolism in Trypanosoma cruzi in the context of human serum-induced apoptotic death. Apoptosis was evidenced by the induction of DNA fragmentation and the inhibition of [ 3 H]thymidine incorporation, which were inhibited by the caspase inhibitor Ac-Asp-Glu-Val-aspartic acid aldehyde (DEVD-CHO). In T. cruzi exposed to death stimuli, supplementation with L-arginine inhibited DNA fragmentation, restored [ 3 H]thymidine incorporation, and augmented parasite ⅐ NO production. These effects were inhibited by the ⅐ NO synthase inhibitor N -nitroarginine methyl ester (L-NAME). Exogenous ⅐ NO limited DNA fragmentation but did not restore proliferation rates. Because L-arginine is also a substrate for arginine decarboxylase (ADC), and its product agmatine is a precursor for polyamine synthesis, we evaluated the contribution of polyamines to limiting apoptosis. Addition of agmatine, putrescine, and the polyamines spermine and spermidine to T. cruzi sustained parasite proliferation and inhibited DNA fragmentation. Also, the ADC inhibitor difluoromethylarginine inhibited L-arginine-dependent restoration of parasite replication rates, while the protection from DNA fragmentation persisted. In aggregate, these results indicate that T. cruzi epimastigotes can undergo programmed cell death that can be inhibited by L-arginine by means of (i) a ⅐ NO synthase-dependent ⅐ NO production that suppresses apoptosis and (ii) an ADC-dependent production of polyamines that support parasite proliferation.

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Differential regulation of putrescine uptake in trypanosoma cruzi and other trypanosomatids

Cited by 30 publications

References 14 publications

The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis

The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis

Trypanosoma cruzi epimastigotes lack ornithine decarboxylase but can express a foreign gene encoding this enzyme

l -Arginine-dependent suppression of apoptosis in Trypanosoma cruzi : Contribution of the nitric oxide and polyamine pathways

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