title: Differential expression on mitochondrial tryparedoxin peroxidase (mTcTXNPx) in Trypanosoma cruzi after ferrocenyl diamine hydrochlorides treatments.
abstract: Resistance to benznidazole in certain strains of Trypanosoma cruzi may be caused by the increased production of enzymes that act on the oxidative metabolism, such as mitochondrial tryparedoxin peroxidase which catalyses the reduction of peroxides. This work presents cytotoxicity assays performed with ferrocenyl diamine hydrochlorides in six different strains of T. cruzi epimastigote forms (Y, Bolivia, SI1, SI8, QMII, and SIGR3). The last four strains have been recently isolated from triatominae and mammalian host (domestic cat). The expression of mitochondrial tryparedoxin peroxidase was analyzed by the Western blotting technique using polyclonal antibody anti mitochondrial tryparedoxin peroxidase obtained from a rabbit immunized with the mitochondrial tryparedoxin peroxidase recombinant protein. All the tested ferrocenyl diamine hydrochlorides were more cytotoxic than benznidazole. The expression of the 25.5kDa polypeptide of mitochondrial tryparedoxin peroxidase did not increase in strains that were more resistant to the ferrocenyl compounds (SI8 and SIGR3). In addition, a 58kDa polypeptide was also recognized in all strains. Ferrocenyl diamine hydrochlorides showed trypanocidal activity and the expression of 25.5kDa mitochondrial tryparedoxin peroxidase is not necessarily increased in some T. cruzi strains. Most likely, other mechanisms, in addition to the over expression of this antioxidative enzyme, should be involved in the escape of parasites from cytotoxic oxidant agents.
authors.affiliation: Universidade Estadual Paulista Júlio de Mesquita Filho, Laboratório de Imunologia e Biologia Molecular, Departamento de Ciências Biológicas, Araraquara, SP, Brazil.
authors.forename: Andréa A N
authors.initials: AA
authors.lastname: Kohatsu
authors.affiliation: Universidade Estadual Paulista Júlio de Mesquita Filho, Laboratório de Imunologia e Biologia Molecular, Departamento de Ciências Biológicas, Araraquara, SP, Brazil.
authors.forename: Flávia A J
authors.initials: FA
authors.lastname: Silva
authors.affiliation: Universidade Federal Fluminense, Instituto de Química, Niterói, RJ, Brazil.
authors.forename: Acácio I
authors.initials: AI
authors.lastname: Francisco
authors.affiliation: Universidade Estadual Paulista "Júlio de Mesquita Filho" Laboratório de Parasitologia, Departamento de Ciências Biológicas, Araraquara, SP, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Rimoldi
authors.affiliation: Universidade de São Paulo, Instituto de Física, São Carlos, SP, Brazil.
authors.forename: Marco T A
authors.initials: MT
authors.lastname: Silva
authors.affiliation: Universidade Federal Fluminense, Instituto de Química, Niterói, RJ, Brazil.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Vargas
authors.affiliation: Universidade Estadual Paulista "Júlio de Mesquita Filho" Laboratório de Parasitologia, Departamento de Ciências Biológicas, Araraquara, SP, Brazil.
authors.forename: João A da
authors.initials: JA
authors.lastname: Rosa
authors.affiliation: Universidade Estadual Paulista Júlio de Mesquita Filho, Laboratório de Imunologia e Biologia Molecular, Departamento de Ciências Biológicas, Araraquara, SP, Brazil. Electronic address: cicarell@fcfar.unesp.br.
authors.forename: Regina M B
authors.initials: RM
authors.lastname: Cicarelli
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002415:Cats; D003959:Diamines / Q000494:pharmacology*; D005296:Ferrous Compounds / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D016877:Oxidants / Q000494:pharmacology*; D010544:Peroxidases / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D011817:Rabbits; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000201:enzymology*
chemical_list: D003959:Diamines; D005296:Ferrous Compounds; D016877:Oxidants; D015800:Protozoan Proteins; D010544:Peroxidases; C110959:tryparedoxin peroxidase
keywords: Ferrocenyl diamine hydrochlorides; Mitochondrial tryparedoxin peroxidase (mTcTXNPx); Oxidative stress mechanisms; Trypanosoma cruzi