Trypanosoma cruzi is the causative agent of Chagas disease (ChD), an endemic disease of public health importance in Latin America that also affects many non-endemic countries due to the increase in migration. This disease affects nearly 8... more
Trypanosoma cruzi is the causative agent of Chagas disease (ChD), an endemic disease of public health importance in Latin America that also affects many non-endemic countries due to the increase in migration. This disease affects nearly 8 million people, with new cases estimated at 50,000 per year. In the 1960s and 70s, two drugs for ChD treatment were introduced: nifurtimox and benznidazole (BZN). Both are effective in newborns and during the acute phase of the disease but not in the chronic phase, and their use is associated with important side effects. These facts underscore the urgent need to intensify the search for new drugs against T. cruzi. T. cruzi is transmitted through hematophagous insect vectors of the Reduviidae and Hemiptera families. Once in the mammalian host, it multiplies intracellularly as the non-flagellated amastigote form and differentiates into the trypomastigote, the bloodstream non-replicative infective form. Inside the insect vector, trypomastigotes transform into the epimastigote stage and multiply through binary fission. This paper describes an assay based on measuring the activity of the cytoplasmic β-galactosidase released into the culture due to parasites lysis by using the substrate, chlorophenol red β-D-galactopyranoside (CPRG). For this, the T. cruzi Dm28c strain was transfected with a β-galactosidase-overexpressing plasmid and used for in vitro pharmacological screening in epimastigote, trypomastigote, and amastigote stages. This paper also describes how to measure the enzymatic activity in cultured epimastigotes, infected Vero cells with amastigotes, and trypomastigotes released from the cultured cells using the reference drug, benznidazole, as an example. This colorimetric assay is easily performed and can be scaled to a high-throughput format and applied to other T. cruzi strains.
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Research Interests:
The CCAAT-binding factor NF-Y (CBF/CP1) is a heteromeric transcription factor involved in the regulation of a variety of eukaryotic genes. We identified NF-Y as the CCAAT activity binding to the promoter region of the gene coding for the... more
The CCAAT-binding factor NF-Y (CBF/CP1) is a heteromeric transcription factor involved in the regulation of a variety of eukaryotic genes. We identified NF-Y as the CCAAT activity binding to the promoter region of the gene coding for the 28-kDa glutathione S-transferase of the human parasite Schistosoma mansoni (Sm28GST). We isolated the NF-YA cDNA from S. mansoni (SmNF-YA): the complete 268 amino acid sequence harbors a region in its C-terminal part that shows homology with the subunit interaction and DNA-binding domains of the mammalian NF-YA; the N-terminal region has an amino acid composition reminiscent of the mammalian and echinoderm counterparts, rich in glutamine and hydrophobic residues, but shows no sequence similarity at the primary level. In vitro synthesized SMNF-YA is able to associate with mammalian NF-YB/C subunits in the absence of DNA and to bind to the Sm28GST CCAAT box. Surprisingly, a monoclonal antibody directed against the non-conserved Q-rich activation domain of mammalian NF-YA supershifts and immunoprecipitates SMNF-YA, strongly suggesting structure conservation in the activation domain between divergent species.
Research Interests: Molecular Biology, Biology, Medicine, Gene expression, Biological Sciences, and 15 morePhylogeny, Mice, Animals, Glutathione, Molecular cloning, Molecular weight, Glutathione Transferase, Monoclonal Antibody, Schistosoma Mansoni, Amino Acid Sequence, Protein Binding, DNA binding proteins, Molecular Sequence Data, Amino acid composition, and Medical and Health Sciences
A set of chemically engineered extracts enriched in compounds including N-N and N-O fragments in their structures was prepared. Bromodomain binding screening and bioguided fractionation led to the identification of one oxime hit that... more
A set of chemically engineered extracts enriched in compounds including N-N and N-O fragments in their structures was prepared. Bromodomain binding screening and bioguided fractionation led to the identification of one oxime hit that interacts with TcBDF3 with affinity in the submicromolar range and that shows interesting antiparasitic properties against the different life cycle stages of T. cruzi.
Research Interests: Pharmacology, Biochemistry, Physiology, Biophysics, Chemistry, and 15 moreInorganic Chemistry, Hematology, Biotechnology, Medicine, Fragment, Identification, Chagas disease, Trypanosoma Cruzi, Extract, Affinity, Enseñanza - Aprendizaje Ciencias Naturales Y Exactas, Antiparasitic activity, Química Orgánica, Compound, and Ciencias Químicas
Research Interests: Medical Microbiology, Biology, Medicine, Gene expression, Immunofluorescence, and 10 moreWestern blotting, Expressed Sequence Tags, Tetracycline, Plasmids, Green Fluorescent Protein, Ciencias Biológicas, Trypanosoma Cruzi, Enseñanza - Aprendizaje Ciencias Naturales Y Exactas, Plasmid, and Restriction Mapping
Research Interests: Biology, Medicine, Humans, Mutation, Ciencias Biológicas, and 13 moreHistones, Protein Domains, Trypanosoma Cruzi, Acetylation, Tubulin, Trypanosomiasis, Protozoan Proteins, Enseñanza - Aprendizaje Ciencias Naturales Y Exactas, Protein Binding, Biochemistry and cell biology, Gene Expression Regulation, BRD, and Medical biochemistry and metabolomics
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Research Interests:
Research Interests:
Research Interests: Molecular Biology, Biology, Medicine, Transcription, Cell line, and 15 moreHumans, Animals, Polymerase Chain Reaction, Glutathione, Gene, Luciferase, HeLa cells, Molecular weight, Glutathione Transferase, Schistosoma Mansoni, Base Sequence, Biochemistry and cell biology, binding sites, Reporter gene, and Medical biochemistry and metabolomics
Bromodomains recognize and bind acetyl-lysine residues present in histone and non-histone proteins in a specific manner. In the last decade they have raised as attractive targets for drug discovery because the miss-regulation of human... more
Bromodomains recognize and bind acetyl-lysine residues present in histone and non-histone proteins in a specific manner. In the last decade they have raised as attractive targets for drug discovery because the miss-regulation of human bromodomains was discovered to be involved in the development of a large spectrum of diseases. However, targeting eukaryotic pathogens bromodomains continues to be almost unexplored. We and others have reported the essentiality of diverse bromodomain- containing proteins in protozoa, offering a new opportunity for the development of antiparasitic drugs, especially for Trypansoma cruzi, the causative agent of Chagas’ disease. Mammalian bromodomains were classified in eight groups based on sequence similarity but parasitic bromodomains are very divergent proteins and are hard to assign them to any of these groups, suggesting that selective inhibitors can be obtained. In this review, we describe the importance of lysine acetylation and bromodomains in T. ...
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Research Interests: Biochemistry, Molecular Biology, Biology, Medicinal Plants, Medicine, and 14 moreEscherichia coli, Glutathione, Glutathione s-transferase, Plasmids, Protein expression and purification, medicinal & Aromatic plants, Fabaceae, Glutathione Transferase, Amino Acid Sequence, Base Sequence, Fusion Protein, Biochemistry and cell biology, Molecular Sequence Data, and Ferredoxin
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Trypanosoma cruzi is a unicellular parasite that causes Chagas disease, which is endemic in the American continent but also worldwide distributed by migratory movements. A striking feature of trypanosomatids is the polycistronic... more
Trypanosoma cruzi is a unicellular parasite that causes Chagas disease, which is endemic in the American continent but also worldwide distributed by migratory movements. A striking feature of trypanosomatids is the polycistronic transcription associated with post-transcriptional mechanisms that regulate the levels of translatable mRNA. In this context, epigenetic regulatory mechanisms have been revealed of great importance, since they are the only ones that would control the access of RNA polymerases to chromatin. Bromodomains are epigenetic protein readers that recognize and specifically bind to acetylated lysine residues, mostly at histone proteins. There are seven coding sequences for BD-containing proteins in trypanosomatids, named TcBDF1 to TcBDF7, and a putative new protein-containing a bromodomain that was recently described. Using the Tet regulated overexpression plasmid pTcINDEX-GW and CRISPR/Cas9 genome editing we were able to demonstrate the essentiality of TcBDF2 in T cr...
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Research Interests:
Research Interests: Microbiology, Biology, Immunohistochemistry, Cell Biology, Medicine, and 15 moreCytoskeleton, Protein Structure and Function, Experimental parasitology, Phylogeny, Animals, Polymerase Chain Reaction, Cluster Analysis, Isoenzymes, Amino Acid Sequence, Polyacrylamide Gel Electrophoresis, Cytoplasm, Intermediate Host, Molecular Sequence Data, Biomphalaria, and Protein Kinase C
En 1940 A. Einstein advirtió que en el futuro “solamente serán exitosos los pueblos que entiendan cómo generar conocimientos y cómo protegerlos; cómo buscar a los jóvenes que tengan la capacidad de hacerlo y asegurarse de que se queden en... more
En 1940 A. Einstein advirtió que en el futuro “solamente serán exitosos los pueblos que entiendan cómo generar conocimientos y cómo protegerlos; cómo buscar a los jóvenes que tengan la capacidad de hacerlo y asegurarse de que se queden en el país. Las otras naciones se quedarán con litorales hermosos, con minas, con una historia espléndida; pero probablemente no se queden ni con las mismas banderas ni fronteras. Y mucho menos con capacidad económica”. Ante esta problemática, en nuestro país hubo diferentes respuestas con mayor o menor grado de formalidad, institucionalización e impactos. Una de ellas en 2007 fue el Programa de Recursos Humanos, con dos componentes: Proyectos de Investigación y Desarrollo para la Radicación de Investigadores (PIDRI) y Proyectos de Formación de Doctores en Áreas Tecnológicas Prioritarias (PFDT). La Universidad Nacional de Rosario presentó un Proyecto que incluyó tres de sus Facultades. El objetivo de este trabajo fue analizar el impacto de los PIDRI c...
<p>*IC<sub>50</sub> was calculated after 72 hs culture.</p><p>ND: not determined.</p><p>IC<sub>50</sub><sup><a... more
<p>*IC<sub>50</sub> was calculated after 72 hs culture.</p><p>ND: not determined.</p><p>IC<sub>50</sub><sup><a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003725#t001fn001" target="_blank">*</a></sup> values of sirtuin inhibitors on <i>T</i>. <i>cruzi</i> Dm28<i>c</i> epimastigotes.</p
: The number of acetylated proteins identified from bacteria to mammals has grown exponentially in the last ten years and it is now accepted that acetylation is a key component in most eukaryotic signaling pathways, as important as... more
: The number of acetylated proteins identified from bacteria to mammals has grown exponentially in the last ten years and it is now accepted that acetylation is a key component in most eukaryotic signaling pathways, as important as phosphorylation. The enzymes involved in this process are well described in mammals; acetyltransferases and deacetylases are found inside and outside the nuclear compartment and have different regulatory functions. In trypanosomatids several of these enzymes have been described and are postulated to be novel antiparasitic targets for the rational design of drugs. In this review article we present an update of the most important known acetylated proteins in trypanosomatids analyzing the acetylomes available. Also, we summarize the information available regarding acetyltransferases and deacetylases in trypanosomes and their potential use as chemotherapeutic targets.
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Trypanosoma cruzi is the causative agent of Chagas disease (ChD), an endemic disease of public health importance in Latin America that also affects many non-endemic countries due to the increase in migration. This disease affects nearly 8... more
Trypanosoma cruzi is the causative agent of Chagas disease (ChD), an endemic disease of public health importance in Latin America that also affects many non-endemic countries due to the increase in migration. This disease affects nearly 8 million people, with new cases estimated at 50,000 per year. In the 1960s and 70s, two drugs for ChD treatment were introduced: nifurtimox and benznidazole (BZN). Both are effective in newborns and during the acute phase of the disease but not in the chronic phase, and their use is associated with important side effects. These facts underscore the urgent need to intensify the search for new drugs against T. cruzi. T. cruzi is transmitted through hematophagous insect vectors of the Reduviidae and Hemiptera families. Once in the mammalian host, it multiplies intracellularly as the non-flagellated amastigote form and differentiates into the trypomastigote, the bloodstream non-replicative infective form. Inside the insect vector, trypomastigotes transform into the epimastigote stage and multiply through binary fission. This paper describes an assay based on measuring the activity of the cytoplasmic β-galactosidase released into the culture due to parasites lysis by using the substrate, chlorophenol red β-D-galactopyranoside (CPRG). For this, the T. cruzi Dm28c strain was transfected with a β-galactosidase-overexpressing plasmid and used for in vitro pharmacological screening in epimastigote, trypomastigote, and amastigote stages. This paper also describes how to measure the enzymatic activity in cultured epimastigotes, infected Vero cells with amastigotes, and trypomastigotes released from the cultured cells using the reference drug, benznidazole, as an example. This colorimetric assay is easily performed and can be scaled to a high-throughput format and applied to other T. cruzi strains.
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Target-directed dynamic combinatorial chemistry (DCC) has emerged as a strategy for the identification of inhibitors of relevant therapeutic targets. In this contribution, we use this strategy for the identification of a high-affinity... more
Target-directed dynamic combinatorial chemistry (DCC) has emerged as a strategy for the identification of inhibitors of relevant therapeutic targets. In this contribution, we use this strategy for the identification of a high-affinity binder of a parasite target, the bromodomain-containing protein BDF3. This protein is essential for viability of , the protozoan parasite that causes Chagas disease. A small dynamic library of acylhydrazones was prepared from aldehydes and acylhydrazides at neutral pH in the presence of aniline. The most amplified library member shows (a) high affinity for the template, (b) interesting antiparasitic activity against different parasite forms, and (c) low toxicity against Vero cells. In addition, parasites are rescued from the compound toxicity by BDF3 overexpression, suggesting that the toxicity of this compound is due to the BDF3 inhibition, i.e., the binding event that initially drives the molecular amplification is reproduced in the parasite, leading...
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A set of chemically engineered extracts enriched in compounds including N-N and N-O fragments in their structures was prepared. Bromodomain binding screening and bioguided fractionation led to the identification of one oxime hit that... more
A set of chemically engineered extracts enriched in compounds including N-N and N-O fragments in their structures was prepared. Bromodomain binding screening and bioguided fractionation led to the identification of one oxime hit that interacts with TcBDF3 with affinity in the submicromolar range and that shows interesting antiparasitic properties against the different life cycle stages of T. cruzi.
Research Interests:
Research Interests:
Research Interests:
SUMMARYThe A subunit of NF-Y nuclear factor from Schistosoma mansoni was expressed in E. coli fused to a histidine tag and purified by affinity chromatography using a Ni2+-Agarose matrix. Antibodies against the recombinant protein were... more
SUMMARYThe A subunit of NF-Y nuclear factor from Schistosoma mansoni was expressed in E. coli fused to a histidine tag and purified by affinity chromatography using a Ni2+-Agarose matrix. Antibodies against the recombinant protein were prepared and used for Western blot and immunolocalization. The presence of SMNF-YA in all stages of the parasite life-cycle was determined by RT-PCR and Western blot analysis. The immunolocalization of SMNF-YA showed the presence of this factor in a parenchymal cell population of cercariae and adult worms and in embryos within eggs. The expression of SMNF-YA was demonstrated to decrease in maturating spermatozoites whereas an accumulation of this factor was observed in the nucleus from oocytes during their maturation processes.
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Acetylation is a ubiquitous protein modification present in prokaryotic and eukaryotic cells that participates in the regulation of many cellular processes. The bromodomain is the only domain known to bind acetylated lysines. In the last... more
Acetylation is a ubiquitous protein modification present in prokaryotic and eukaryotic cells that participates in the regulation of many cellular processes. The bromodomain is the only domain known to bind acetylated lysines. In the last years many bromodomain inhibitors have been developed in order to treat diseases caused by aberrant acetylation of lysine residues and have been tested as anti-parasitic drugs. Here, we report the first characterization of T. cruzi Bromodomain Factor 1. Tc BDF1 is expressed in all life cycle stages but it is developmentally regulated. It localizes in the glycosomes directed by a PTS2 sequence. The overexpression of Tc BDF1 wild type is detrimental for epimastigotes, but it enhances the infectivity rate of trypomastigotes and the replication of amastigotes. On the other hand, the overexpression of a mutated version of Tc BDF1 has no effect on epimastigotes, but it does negatively affect on trypomastigotes' infection and amastigotes' replication.
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Research Interests:
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We have cloned from Biomphalaria glabrata, the intermediate host of the helminth parasite Schistosoma mansoni, a 36-kDa apparent-molecular-mass molecule (BgSel) that shares sequence identity with selectins of the cell-adhesion-molecule... more
We have cloned from Biomphalaria glabrata, the intermediate host of the helminth parasite Schistosoma mansoni, a 36-kDa apparent-molecular-mass molecule (BgSel) that shares sequence identity with selectins of the cell-adhesion-molecule superfamily. BgSel exhibited in its C-terminal part a putative C-type lectin domain similar to the selectin lectin domain. Using antibodies to the recombinant BgSel protein, we demonstrated the presence of BgSel in snail hemocytes as well as in the cell line derived from B. glabrata embryos (Bge). Anti-BgSel antibodies specifically recognized a 79-kDa component in Bge-cell-secreted products that was supposed to represent the native form of BgSel, as was confirmed after glycosidase treatment. Lectins are known to be implicated in recognition mechanisms participating in humoral and cellular immunity in molluscs. The possible role of BgSel in the interaction between sporocysts and Bge cells, particularly in the in vitro model of sporocyst development dependent on Bge cell factors, remains to be determined.
Research Interests: Microbiology, Parasitology, Medical Microbiology, Biology, Medicine, and 15 moreCell line, Animals, Lectins, Molecular cloning, Cellular Immunity, Molecular Mass, Veterinary Sciences, Schistosoma Mansoni, Amino Acid Sequence, Base Sequence, Recombinant Proteins, Embryos, Selectins, Molecular Sequence Data, and Biomphalaria
... Bge cells can provide good environmental conditions for the development of mother sporocysts to the daughter form (Yoshino and Laursen 1995). ... The plasmid pDr-luc contained the luci-ferase gene under the control of the... more
... Bge cells can provide good environmental conditions for the development of mother sporocysts to the daughter form (Yoshino and Laursen 1995). ... The plasmid pDr-luc contained the luci-ferase gene under the control of the heat-shock-respon-sive element from the Drosophila ...
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The ability of the 5&#39; flanking region of the gene encoding the 28 kDa glutathione S-transferase of Schistosoma mansoni gene to promote transcription, was studied in different mammalian cell lines. Results of transient transfection... more
The ability of the 5&#39; flanking region of the gene encoding the 28 kDa glutathione S-transferase of Schistosoma mansoni gene to promote transcription, was studied in different mammalian cell lines. Results of transient transfection assays showed a strong activity of the -277 to +1 nt region of the Sm28GST gene, comparable to that of well-studied promoters. Deletion analysis indicated that an AP-1 site and two closely located CCAAT (Y1 and Y2) boxes were the principal motifs responsible for the promoter activity. Binding of the NF-Y complex to Y1 and Y2, as well as to a third CCAAT box (Y3) close to the promoter TATA box, was compared in gel shift and super-shift experiments. All of the three Y boxes bound protein complexes from S. mansoni nuclear extracts that were shown to contain the A subunit of the schistosome NF-Y complex (SMNF-YA). Competition assays revealed a differential affinity of the Y1, Y2 and Y3 sequences for NF-Y. The Y1, Y2 and Y3 regions were also shown to activate transcription when included in an heterologous promoter and data obtained strongly suggested the involvement of SMNF-Y in multimeric complexes during this process.
Research Interests: Functional Analysis, Biology, Transcription Factors, Medicine, Biological Sciences, and 13 moreCell line, Animals, Glutathione, Transcription Factor, Protein Complex Detection, Protein Conformation, Glutathione Transferase, Schistosoma Mansoni, Protein Binding, DNA binding proteins, Gene Expression Regulation, Reporter gene, and Medical and Health Sciences
Research Interests: Immunohistochemistry, Transcription Factors, Biological Sciences, Humans, Mice, and 12 moreAnimals, Cyclosporine, Helminth, Transcription Factor, Glutathione Transferase, S100 protein family, Schistosoma Mansoni, Rabbits, Base Sequence, DNA binding proteins, Molecular Sequence Data, and Medical and Health Sciences
The CCAAT-binding factor NF-Y (CBF/CP1) is a heteromeric transcription factor involved in the regulation of a variety of eukaryotic genes. We identified NF-Y as the CCAAT activity binding to the promoter region of the gene coding for the... more
The CCAAT-binding factor NF-Y (CBF/CP1) is a heteromeric transcription factor involved in the regulation of a variety of eukaryotic genes. We identified NF-Y as the CCAAT activity binding to the promoter region of the gene coding for the 28-kDa glutathione S-transferase of the human parasite Schistosoma mansoni (Sm28GST). We isolated the NF-YA cDNA from S. mansoni (SmNF-YA): the complete 268 amino acid sequence harbors a region in its C-terminal part that shows homology with the subunit interaction and DNA-binding domains of the mammalian NF-YA; the N-terminal region has an amino acid composition reminiscent of the mammalian and echinoderm counterparts, rich in glutamine and hydrophobic residues, but shows no sequence similarity at the primary level. In vitro synthesized SMNF-YA is able to associate with mammalian NF-YB/C subunits in the absence of DNA and to bind to the Sm28GST CCAAT box. Surprisingly, a monoclonal antibody directed against the non-conserved Q-rich activation domain of mammalian NF-YA supershifts and immunoprecipitates SMNF-YA, strongly suggesting structure conservation in the activation domain between divergent species.
Research Interests: Biology, Medicine, Gene expression, Biological Sciences, Phylogeny, and 15 moreSequence alignment, Mice, Animals, Glutathione, Molecular cloning, Molecular weight, Glutathione Transferase, Monoclonal Antibody, Schistosoma Mansoni, Amino Acid Sequence, Protein Binding, DNA binding proteins, Molecular Sequence Data, Amino acid composition, and Medical and Health Sciences
ABSTRACT A new series of secondary and tertiary amines were prepared by reductive amination of synthetic phenyl-butyraldehydes and evaluated for their in vitro activity against Trypanosoma cruzi. © 2012 The Royal Society of Chemistry.
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Research Interests:
Research Interests:
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ABSTRACTBromodomains are highly conserved acetyl-lysine binding domains found mainly in proteins associated with chromatin and nuclear acetyltransferases. TheTrypanosoma cruzigenome encodes at least four bromodomain factors (TcBDFs). We... more
ABSTRACTBromodomains are highly conserved acetyl-lysine binding domains found mainly in proteins associated with chromatin and nuclear acetyltransferases. TheTrypanosoma cruzigenome encodes at least four bromodomain factors (TcBDFs). We describe here bromodomain factor 3 (TcBDF3), a bromodomain-containing protein localized in the cytoplasm.TcBDF3 cytolocalization was determined, using purified antibodies, by Western blot and immunofluorescence analyses in all life cycle stages ofT. cruzi. In epimastigotes and amastigotes, it was detected in the cytoplasm, the flagellum, and the flagellar pocket, and in trypomastigotes only in the flagellum. Subcellular localization ofTcBDF3 was also determined by digitonin extraction, ultrastructural immunocytochemistry, and expression ofTcBDF3 fused to cyan fluorescent protein (CFP). Tubulin can acquire different posttranslational modifications, which modulate microtubule functions. Acetylated α-tubulin has been found in the axonemes of flagella an...
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© 2009 Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas, 8 (3), 211 - 218 ... Trypanocide activity of Castela coccinea Griseb. extracts ... [Actividad tripanocida de extractos de Castela coccinea Griseb.] ... María... more
© 2009 Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas, 8 (3), 211 - 218 ... Trypanocide activity of Castela coccinea Griseb. extracts ... [Actividad tripanocida de extractos de Castela coccinea Griseb.] ... María L. MARTÍNEZa*, María NOEL ...
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Trypanosomatids have a cytoskeleton arrangement that is simpler than what is found in most eukaryotic cells. However, it is precisely organized and constituted by stable microtubules. Such microtubules compose the mitotic spindle during... more
Trypanosomatids have a cytoskeleton arrangement that is simpler than what is found in most eukaryotic cells. However, it is precisely organized and constituted by stable microtubules. Such microtubules compose the mitotic spindle during mitosis, the basal body, the flagellar axoneme and the subpellicular microtubules, which are connected to each other and also to the plasma membrane forming a helical arrangement along the central axis of the parasite cell body. Subpellicular, mitotic and axonemal microtubules are extensively acetylated in Trypanosoma cruzi. Acetylation on lysine (K) 40 of α-tubulin is conserved from lower eukaryotes to mammals and is associated with microtubule stability. It is also known that K40 acetylation occurs significantly on flagella, centrioles, cilia, basal body and the mitotic spindle in eukaryotes. Several tubulin posttranslational modifications, including acetylation of K40, have been catalogued in trypanosomatids, but the functional importance of these...
Many glomerular diseases are associated with changes in the expression and distribution in the components of extracellular matrix. A remarkable feature in acute renal failure induced by mercuric chloride in rats was large fibronectin (Fn)... more
Many glomerular diseases are associated with changes in the expression and distribution in the components of extracellular matrix. A remarkable feature in acute renal failure induced by mercuric chloride in rats was large fibronectin (Fn) deposits in kidneys 1 h post-HgCl2 injection (5 mg/kg body wt., s.c.). Our study examined some mechanisms as potential explanation of the early Fn deposits in mercuric chloride induced acute renal failure. Total tissue mRNA of livers and kidneys of control and treated rats were used in Northern blot to determine whether accumulation of Fn in kidney is associated with increases in the expression of this protein in the kidney and/or in the liver. Analysis of Fn levels by Western blot were also performed. Northern blot did not show significant difference between control and treated rats, while the abundance of polymerized-Fn in kidney tissue was increased 1 h and 5 h post HgCl2 injection. HgCl2 influence on Fn folding was studied in vitro to detect po...
Research Interests: Protein Folding, Kinetics, Acute kidney injury, Immunohistochemistry, Extracellular Matrix, and 20 moreWestern blotting, Acute renal failure, Molecular and cellular biology, Humans, Kidney, Liver, Animals, Male, Temperature, Disinfectants, Gelatin, Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis, Rats, Time Factors, Western blot, Wistar Rats, Binding Site, Conformational Change, Molecular and Cellular Biochemistry, and Biochemistry and cell biology
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AGRIS record. Record number, GB9407840. Titles, The path of chromoplast development in fruits and flowers. Personal Authors, Marano, MR,Serra, EC,Orellano, EG,Carrillo, N. (Departamento de Ciencias Biologicas, Area Biologia ...
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Research Interests: Sequence Analysis, Biological Sciences, Environmental Sciences, Humans, Mice, and 14 moreAnimals, T cells, Nucleic Acids, Transcription Factor, Molecular cloning, HeLa cells, Amino Acid Profile, Transfection, Protein Conformation, Schistosoma Mansoni, Amino Acid Sequence, Base Sequence, Protein Binding, and DNA binding proteins
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Trypanosoma cruzi is a protozoan pathogen responsible for Chagas disease. Current therapies are inadequate because of their severe host toxicity and numerous side effects. The identification of new biotargets is essential for the... more
Trypanosoma cruzi is a protozoan pathogen responsible for Chagas disease. Current therapies are inadequate because of their severe host toxicity and numerous side effects. The identification of new biotargets is essential for the development of more efficient therapeutic alternatives. Inhibition of sirtuins from Trypanosoma brucei and Leishmania ssp. showed promising results, indicating that these enzymes may be considered as targets for drug discovery in parasite infection. Here, we report the first characterization of the two sirtuins present in T. cruzi. Dm28c epimastigotes that inducibly overexpress TcSIR2RP1 and TcSIR2RP3 were constructed and used to determine their localizations and functions. These transfected lines were tested regarding their acetylation levels, proliferation and metacyclogenesis rate, viability when treated with sirtuin inhibitors and in vitro infectivity. TcSIR2RP1 and TcSIR2RP3 are cytosolic and mitochondrial proteins respectively. Our data suggest that s...