In vivo effects of sodium chlorate on cruzipain sulfation in epimastigote forms of Trypanosoma cruzi.

M. R. FERRERO; L.L. SOPRANO; D. M. ACOSTA; G. A. GARCÍA; A. S. COUTO; V G. DUSCHAK

Santa Fé- Argentina

Congreso; XXIII REUNION Científica ANUAL SOC. ARG.de Protozoología.; 2009

SOC. ARG.de Protozoología

In vivo effects of sodium chlorate on cruzipain sulfation in epimastigote forms of Trypanosoma cruzi. Maximiliano R. Ferrero, Luciana Lia Soprano, Diana M. Acosta, Gabriela A. García, Alicia S. Couto and Vilma G. Duschak Trypanosoma cruzi, the parasitic protozoan that causes Chagas disease, contains a major cysteine proteinase, cruzipain. This lysosomal enzyme bears an unusual C-terminal extension that contains a number of post-translational modifications. We have reported the presence of sulfated structures in the C-T domain of this glycoprotein, constituting the first report on the presence of a sulfated glycoprotein in Tripanosomatids. Sulfotransferases (STs) catalize the transfer reaction of the sulfate group from the ubiquitous donor 3´phosphoadenosine 5`phosphosulfate (PAPS) to an acceptor group of numerous substrates. This reaction often referred to as sulfuryl transfer, sulfation or sulfonation, is widely observed from bacteria to humans and plays a key role in various biological processes such as cell communication, growth and development as well as   defence. Chlorate is known to be an in vitro inhibitor of ATP–sulfurylase, the first enzyme in the biosynthesis of PAPS which is the ubiquitous co-substrate for sulfation which has been used to abolish protein sulfation on tyrosine as well as on carbohydrate residues in intact cells. In this work, we have examined the in vivo effect of chlorate on cruzipain sulfation in epimastigote forms of T. cruzi.  Epimastigotes were treated with growing concentrations of sodium chlorate (10-80 mM) during 24, 48 and 96 h. The results, showed a significant decrease in the immunerecognition of specific antisulfate antibodies, obtained from mice immunized with Cz followed by absorption with desulfated cruzipain. It is worth stressing that there are no putative genes for canonic sulfotransferases identified up to now in the T. cruzi genome. This fact supports the thesis that significant differences in sequences between T. cruzi and mammalian sulfotransferases exist. So, it could be feasible to take advantage of these differences to consider these enzymes as valid targets for chemotherapeutic drug design. Supported by CONICET-ANPCYT-UBA, INP-ANLIS-Malbrán