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Changes in spermine levels are involved in the effects of phorbol ester (12-O-tetradecanoylphorbol-13-acetate) and dibutyryl cAMP on the growth of Trypanosoma cruzi

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The effects of tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), cAMP analogue dibutyryl cAMP (DB) and histamine were studied on arginine decarboxylase activity, polyamine content and growth rate of Trypanosoma cruzi, RA strain epimastigotes. TPA enhanced all these parameters at the early logarithmic phase of parasite grown in two succesive passages through a polyamine free medium. The stimulatory action of TPA was blocked by inhibitors of transcription (actinomycin D), protein synthesis (cycloheximide) and polyamine synthesis (α-DL-difluoromethylarginine and cyclohexylamine). Spermine abolished arginine decarboxylase activity and increased the proliferative rate of both control and TPA-treated epimastigotes. In contrast DB reduced all studied parameters, suggesting a role for spermine decrease in the cAMP-mediated differentiation to trypomastigote. These results provide evidence that changes in spermine content could be involved in the signal transduction mechanisms, which control both proliferation and differentiation. Histamine could not fulfil spermine roles.


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