Intracellular cyclic AMP levels modulate differential adaptive responses on epimastigotes and cell culture trypomastigotes of Trypanosoma cruzi

STERNLIEB T; SCHOIJET, A.C.; ALONSO, G.D.

ACTA TROPICA

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2019

0001-706X

Among the many environmental challenges the parasite Trypanosoma cruzi has toovercome to complete its life cycle through different hosts, oxidative stress plays a centralrole. Different stages of this parasite encounter distinct sources of oxidative stress, such asthe oxidative burst of the immune system, or the Heme released from hemoglobindegradation in the triatomine‟s midgut. Also, the redox status of the surroundings functionsas a signal to the parasite, triggering processes coupled to differentiation or proliferation.Intracellular second messengers, like cAMP, are responsible for the transduction ofenvironmental queues and initiating cellular processes accordingly. In trypanosomatidscAMP is involved in a variety of processes, including proliferation, differentiation,osmoregulation and quorum sensing. Trypanosomatid phosphodiesterases (PDE) showatypical pharmacological properties and some have been involved in key processes for thesurvival of the parasites, which validates them as attractive therapeutic targets. Our workhere shows that cAMP modulates different processes according to parasite stage.Epimastigotes become more resistant to oxidative stress when pre-treated with cAMP analogs, while in trypomastigotes an increase in intracellular cAMP doesn‟t seem to aid inthis response, although it does increase the number of amastigotes obtained 48 h afterinfection, compared to the control group. Also, we show that TcrPDEA1, a functionallyenigmatic phosphodiesterase with very high Km, is involved in the epimastigotes responseto oxidative stress.