title: Nitric oxide affects trypomastigote to amastigote differentiation in Trypanosoma cruzi.
abstract: Trypanosoma cruzi is the etiologic agent of Chagas disease. Two main distinct forms are present in the mammalian host: trypomastigote, an infective form, and the amastigote, a typical replicative form. Succeeding the host cell invasion, trypomastigotes differentiate to amastigotes, a process known as amastigogenesis. Amastigogenesis is characterized by parasite body remodeling, with drastic reduction of flagellum, and changes in protein profile and energetic metabolism. Our aim is to explore the role of nitric oxide as a signaling molecule during the amastigogenesis process, which must be strictly regulated. We report herein that acid pH (6.0) is essential for T. cruzi amastigogenesis. Also, during amastigogenesis there is a progressive solubilization of the paraflagellar protein, a flagellum marker. Moreover, the process is dependent on (•)NO concentration, since it is suppressed by 1mM SNAP, a (•)NO donor, and favored by 10mM L-NAME, a NOS inhibitor. Accordingly, S-nitrosylation of selective proteins occurs in amastigogenesis. Additionally, amastigogenesis is affected by IBMX (PDE inhibitor) treatment, suggesting the importance of cyclic nucleotides signaling. Furthermore, tubulin stability is also affected by the (•)NO availability. Along amastigogenesis, flagellum disassembling is accompanied by changes in a-tubulin tyrosylation and polyglutamylation levels. Taken together, these results suggest (•)NO participation in trypomastigote differentiation to amastigotes in T. cruzi.
authors.affiliation: University of Sao Paulo (Institute of Chemistry), Department of Biochemistry, Brazil.
authors.forename: Chrislaine O
authors.initials: CO
authors.lastname: Soares
authors.affiliation: Faculdades Oswaldo Cruz (Biological Sciences ), Pharmaceutical Sciences, Brazil.
authors.forename: Caroline P
authors.initials: CP
authors.lastname: Dias
authors.affiliation: University of Sao Paulo (Institute of Chemistry), Department of Biochemistry, Brazil.
authors.forename: Walter
authors.initials: W
authors.lastname: Colli
authors.affiliation: University of Sao Paulo (Institute of Chemistry), Department of Biochemistry, Brazil. Electronic address: chris0bio@gmail.com.
authors.forename: M Julia
authors.initials: MJ
authors.lastname: Manso Alves