Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole

Autor: Juciane Vaz do Rego, Francirlene de Carvalho Sousa, Silvane M. F. Murta, Ana Paula Duarte, Humberto Medeiros Barreto, Daniel Barbosa Liarte, Jacqueline Bua, Gandhi Rádis-Baptista, Alvaro J. Romanha
Jazyk: angličtina
Rok vydání: 2015
Předmět:
CIENCIAS MÉDICAS Y DE LA SALUD
Trypanosoma cruzi
Immunology
Population
Drug Resistance
Gene Dosage
Biology
Tecnologías que involucran la identificación de ADN
proteínas y enzimas
y cómo influyen en el conjunto de enfermedades y mantenimiento del bienestar
Biotecnología de la Salud
Cyclophilins
parasitic diseases
medicine
Ciclofilinas
Northern blot
Amino Acid Sequence
RNA
Messenger
purl.org/becyt/ford/3.4 [https]
education
Gene
Cyclophilin
Phylogeny
Southern blot
Genetics
education.field_of_study
sobreexpresion de TcCyP19
Chromosome Mapping
General Medicine
Sequence Analysis
DNA
DNA
Protozoan
biology.organism_classification
Molecular biology
Trypanocidal Agents
resistencia benznidazol
Infectious Diseases
Real-time polymerase chain reaction
Gene Expression Regulation
Benznidazole
Nitroimidazoles
Parasitology
purl.org/becyt/ford/3 [https]
Genome
Protozoan
Sequence Alignment
RNA
Protozoan
medicine.drug
Zdroj: CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Popis: Cyclophilin (TcCyP19), a peptidyl-prolyl cis/trans isomerase, is a key molecule with diverse biological functions that include roles in molecular chaperoning, stress response, immune modulation, and signal transduction. In this respect, TcCyP19 could serve as a potential drug target in diseasecausing parasites. Previous studies employing proteomics techniques have shown that the TcCyP19 isoform was more abundant in a benznidazole (BZ)-resistant Trypanosoma cruzi population than in its susceptible counterpart. In this study, TcCyP19 has been characterized in BZ-susceptible and BZresistant T. cruzi populations. Phylogenetic analysis revealed a clear dichotomy between Cyphophilin A (CyPA) sequences from trypanosomatids and mammals. Sequencing analysis revealed that the amino acid sequences of TcCyP19 were identical among the T. cruzi samples analyzed. Southern blot analysis showed that TcCyP19 is a single-copy gene, located in chromosomal bands varying in size from 0.68 to 2.2 Mb, depending on the strain of T. cruzi. Northern blot and qPCR indicated that the levels of TcCyP19 mRNA were two-fold higher in drug-resistant T. cruzi populations than in their drugsusceptible counterparts. Similarly, as determined by two-dimensional gel electrophoresis immunoblot, the expression of TcCyP19 protein was increased to the same degree in BZ-resistant T. cruzi populations. No differences in TcCyP19 mRNA and protein expression levels were observed between the susceptible and the naturally resistant T. cruzi strains analyzed. Taken together, these data indicate that cyclophilin TcCyP19 expression is up-regulated at both transcriptional and translational levels in T. cruzi populations that were in vitro-induced and in vivo-selected for resistance to BZ. Fil: Rêgo, Juciane Vaz. Universidade Federal Do Piaui.; Brasil Fil: Duarte, Ana Paula. Fundación Oswaldo Cruz; Brasil Fil: Liarte, Daniel Barbosa. Universidade Federal Do Piaui.; Brasil Fil: de Carvalho Sousa, Francirlene. Universidade Federal Do Piaui.; Brasil Fil: Barreto, Humberto Medeiros. Universidade Federal Do Piaui.; Brasil Fil: Bua, Jacqueline Elena. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Romanha, Alvaro José. Fundación Oswaldo Cruz; Brasil Fil: Rádis Baptista, Gandhi. Universidade Federal Do Piaui.; Brasil Fil: Murta, Silvane Maria Fonseca. Universidade Federal Do Piaui.; Brasil
Databáze: OpenAIRE
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