Pub Date : 2010-12-10DOI: 10.2174/1874421401004010148
A. Ávila, S. Goldenberg
The regulation of gene expression in trypanosomatids is predominantly post-transcriptional. Polycistronic tran- scripts are processed by the addition of a common 5'-spliced leader and polyadenylation. However, the processed mRNAs are not necessarily functionally related, suggesting the existence of mechanisms for the degradation or storage of untrans- latable mRNAs. Determination of the TriTryps (Leishmania major, Trypanosoma brucei and Trypanosoma cruzi) genome sequences has allowed the identification of genes encoding potential regulatory proteins. This review discusses some of the mechanisms and regulatory elements involved in cytoplasmic gene expression regulation in Trypanosoma cruzi. We also discuss how functional genomic tools have contributed toward determining the role played by RNA binding protein complexes, supporting the concept of "post-transcriptional RNA operons" or "RNA regulons". This suggests the existence of interconnected regulatory networks in the parasite, in which RNA granules act as protagonists in cytoplasmic mRNA metabolism.
{"title":"Functional Genomics and Insights into Trypanosoma cruzi Gene ExpressionRegulation","authors":"A. Ávila, S. Goldenberg","doi":"10.2174/1874421401004010148","DOIUrl":"https://doi.org/10.2174/1874421401004010148","url":null,"abstract":"The regulation of gene expression in trypanosomatids is predominantly post-transcriptional. Polycistronic tran- scripts are processed by the addition of a common 5'-spliced leader and polyadenylation. However, the processed mRNAs are not necessarily functionally related, suggesting the existence of mechanisms for the degradation or storage of untrans- latable mRNAs. Determination of the TriTryps (Leishmania major, Trypanosoma brucei and Trypanosoma cruzi) genome sequences has allowed the identification of genes encoding potential regulatory proteins. This review discusses some of the mechanisms and regulatory elements involved in cytoplasmic gene expression regulation in Trypanosoma cruzi. We also discuss how functional genomic tools have contributed toward determining the role played by RNA binding protein complexes, supporting the concept of \"post-transcriptional RNA operons\" or \"RNA regulons\". This suggests the existence of interconnected regulatory networks in the parasite, in which RNA granules act as protagonists in cytoplasmic mRNA metabolism.","PeriodicalId":89294,"journal":{"name":"The open parasitology journal","volume":"17 1","pages":"148-155"},"PeriodicalIF":0.0,"publicationDate":"2010-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77881472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-12-10DOI: 10.2174/1874421401004010060
J. Scharfstein
Trypanosoma cruzi proteases were object of intensive structural and functional characterization in the past de- cades. The celebration of the Chagas disease centenarian makes it opportune to review the foundations of molecular re- search on cruzipain, a major lysosomal cysteine protease. Acting as a virulence factor, cruzipain promotes intracellular parasitism. In addition, tissue culture trypomastigotes (TCTs) exploit the enzymatic versatility of cruzipain to liberate kinin peptides from kininogen molecules associated to heparan sulfate proteoglycans. Acting as paracrine agonists, the re- leased kinins (eg, lysyl-bradykinin) potentiate parasite invasion of cardiovascular cells through the signaling of hetero- trimeric G-protein coupled bradykinin receptors (BKRs). Generation of kinins also stimulates immunity, implying that cruzipain activity brings mutual benefits for the host-parasite relationship. Analysis of the dynamics of inflammation re- vealed that TCTs induce secretion of KC/MIP-2 by macrophages via signaling of Toll-like 2 receptors (TLR2). Acting on proximal microvascular beds, CXC chemokines evoke plasma extravasations by activating endothelium/neutrophils via CXCR2. Diffusion of plasma proteins (including kininogens) through extracellular matrices allow for cruzipain-dependent generation of vasoactive kinins, which then intensify interstitial edema through the activation of endothelial BK2R. Extent of edematogenic inflammation is counter-regulated by angiotensin converting enzyme (ACE), a kinin-degrading metal- lopeptidase. Acting at the interface between the vascular and the immune systems, kinins activate BK2R of dendritic cells, which then migrate to T- cell rich areas of secondary lymphoid tissues, where they induce immunoprotective type-1 effec- tor T cells. Insight into the mechanisms regulating proteolysis in extravascular sites of infection may help to identify sus- ceptibility markers of chronic heart disease.
{"title":"Trypanosoma cruzi Cysteine Proteases, Acting at the Interface Between the Vascular and Immune Systems, Influence Pathogenic Outcome in Experimental Chagas Disease","authors":"J. Scharfstein","doi":"10.2174/1874421401004010060","DOIUrl":"https://doi.org/10.2174/1874421401004010060","url":null,"abstract":"Trypanosoma cruzi proteases were object of intensive structural and functional characterization in the past de- cades. The celebration of the Chagas disease centenarian makes it opportune to review the foundations of molecular re- search on cruzipain, a major lysosomal cysteine protease. Acting as a virulence factor, cruzipain promotes intracellular parasitism. In addition, tissue culture trypomastigotes (TCTs) exploit the enzymatic versatility of cruzipain to liberate kinin peptides from kininogen molecules associated to heparan sulfate proteoglycans. Acting as paracrine agonists, the re- leased kinins (eg, lysyl-bradykinin) potentiate parasite invasion of cardiovascular cells through the signaling of hetero- trimeric G-protein coupled bradykinin receptors (BKRs). Generation of kinins also stimulates immunity, implying that cruzipain activity brings mutual benefits for the host-parasite relationship. Analysis of the dynamics of inflammation re- vealed that TCTs induce secretion of KC/MIP-2 by macrophages via signaling of Toll-like 2 receptors (TLR2). Acting on proximal microvascular beds, CXC chemokines evoke plasma extravasations by activating endothelium/neutrophils via CXCR2. Diffusion of plasma proteins (including kininogens) through extracellular matrices allow for cruzipain-dependent generation of vasoactive kinins, which then intensify interstitial edema through the activation of endothelial BK2R. Extent of edematogenic inflammation is counter-regulated by angiotensin converting enzyme (ACE), a kinin-degrading metal- lopeptidase. Acting at the interface between the vascular and the immune systems, kinins activate BK2R of dendritic cells, which then migrate to T- cell rich areas of secondary lymphoid tissues, where they induce immunoprotective type-1 effec- tor T cells. Insight into the mechanisms regulating proteolysis in extravascular sites of infection may help to identify sus- ceptibility markers of chronic heart disease.","PeriodicalId":89294,"journal":{"name":"The open parasitology journal","volume":"35 1","pages":"60-71"},"PeriodicalIF":0.0,"publicationDate":"2010-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90543784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-12-10DOI: 10.2174/1874421401004010188
M. Silva-Neto, P. Fampa, Carlo Donato Caiaffa-Neto, A. Carneiro, G. Atella
The year 2009 is the centennial anniversary of the original description of Chagas disease by Carlos Chagas. During the last 100 years, several advances have occurred regarding our knowledge of the development of Trypanosoma cruzi and its travel along the gut of Triatominae vectors. We have also witnessed the completion of both the human and parasite genome projects; the genome of one of Chagas disease vectors, Rhodnius prolixus, is currently being sequenced. The development of T. cruzi in triatomine gut relies on several biochemical and molecular processes. The biochemistry of blood digestion and the molecular and biological aspects of parasite development are well known. However, several sig- naling molecules are generated during blood digestion, and their effects on parasite biology are only beginning to be un- derstood. Here, we will summarize our current knowledge in this area with an emphasis on heme and bioactive lipids. In addition, we will highlight some recently described members of the parasite signaling machinery, which were identified through high-throughput studies, but whose ligands are unknown thus far. Finally, we will discuss some potential aspects for future investigation in this area that may strengthen our view of such a concomitant biological process in the next years.
{"title":"Cell Signaling During Trypanosoma cruzi Development in Triatominae","authors":"M. Silva-Neto, P. Fampa, Carlo Donato Caiaffa-Neto, A. Carneiro, G. Atella","doi":"10.2174/1874421401004010188","DOIUrl":"https://doi.org/10.2174/1874421401004010188","url":null,"abstract":"The year 2009 is the centennial anniversary of the original description of Chagas disease by Carlos Chagas. During the last 100 years, several advances have occurred regarding our knowledge of the development of Trypanosoma cruzi and its travel along the gut of Triatominae vectors. We have also witnessed the completion of both the human and parasite genome projects; the genome of one of Chagas disease vectors, Rhodnius prolixus, is currently being sequenced. The development of T. cruzi in triatomine gut relies on several biochemical and molecular processes. The biochemistry of blood digestion and the molecular and biological aspects of parasite development are well known. However, several sig- naling molecules are generated during blood digestion, and their effects on parasite biology are only beginning to be un- derstood. Here, we will summarize our current knowledge in this area with an emphasis on heme and bioactive lipids. In addition, we will highlight some recently described members of the parasite signaling machinery, which were identified through high-throughput studies, but whose ligands are unknown thus far. Finally, we will discuss some potential aspects for future investigation in this area that may strengthen our view of such a concomitant biological process in the next years.","PeriodicalId":89294,"journal":{"name":"The open parasitology journal","volume":"241 1","pages":"188-194"},"PeriodicalIF":0.0,"publicationDate":"2010-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73644110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-12-10DOI: 10.2174/1874421401004010167
I. C. Almeida, E. Nakayasu
One century after the discovery of Chagas disease, the treatment for this illness is still based only on two drugs with limited efficacy and severe side effects. In this mini-review, we discuss the application of mass spectrometry (MS)- based proteomic approaches to study the biochemistry and cell biology of etiologic agent of Chagas disease, Trypanosoma cruzi. We focus the discussion in the analysis of subcellular proteomics and posttranslational modifications (PTMs). In re- cent years, subcellular proteomics has brought new insights into the localization of proteins and possible functions of or- ganelles. Thus far, proteomic analysis of reservosomes, ribosomes, detergent-solubilized membranes, and a preparation of an organelle mixture have been performed. In addition, a number of analyses of PTMs of T. cruzi proteins (i.e., histone modifications, phosphorylation, glycosylation, glycosylphosphatidylinositol (GPI)-anchoring, and nitrosylation) have been successfully carried out. The identification of those and other PTMs combined with cutting-edge biochemical, im- munological and cell biology approaches, have allowed a more in-depth understanding of biological and pathophysiologi- cal processes resulting from host cell-parasite interactions.
{"title":"Subcellular proteomics and global analysis of posttranslational modifications to study functional roles of Trypanosoma cruzi molecules","authors":"I. C. Almeida, E. Nakayasu","doi":"10.2174/1874421401004010167","DOIUrl":"https://doi.org/10.2174/1874421401004010167","url":null,"abstract":"One century after the discovery of Chagas disease, the treatment for this illness is still based only on two drugs with limited efficacy and severe side effects. In this mini-review, we discuss the application of mass spectrometry (MS)- based proteomic approaches to study the biochemistry and cell biology of etiologic agent of Chagas disease, Trypanosoma cruzi. We focus the discussion in the analysis of subcellular proteomics and posttranslational modifications (PTMs). In re- cent years, subcellular proteomics has brought new insights into the localization of proteins and possible functions of or- ganelles. Thus far, proteomic analysis of reservosomes, ribosomes, detergent-solubilized membranes, and a preparation of an organelle mixture have been performed. In addition, a number of analyses of PTMs of T. cruzi proteins (i.e., histone modifications, phosphorylation, glycosylation, glycosylphosphatidylinositol (GPI)-anchoring, and nitrosylation) have been successfully carried out. The identification of those and other PTMs combined with cutting-edge biochemical, im- munological and cell biology approaches, have allowed a more in-depth understanding of biological and pathophysiologi- cal processes resulting from host cell-parasite interactions.","PeriodicalId":89294,"journal":{"name":"The open parasitology journal","volume":"17 1","pages":"167-177"},"PeriodicalIF":0.0,"publicationDate":"2010-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73095498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-12-10DOI: 10.2174/1874421401004010116
J. Meyer‐Fernandes, D. Cosentino-Gomes, Danielle P. Vieira, A. Lopes
Ecto-nucleoside triphosphate diphosphohydrolases (ecto-NTPDases), also known as ecto-ATPases and/or ecto- apyrases, are integral membrane glycoproteins or soluble enzymes that are dependent on divalent cations. These ecto- enzymes are important ecto-nucleotidases that are characterized by the ability to hydrolyze nucleoside triphosphates and nucleoside diphosphates to the monophosphate form. The hydrolysis of nucleoside monophosphates to nucleosides such as adenosine may then be catalyzed by the action of ecto-5´nucleotidases. The present study reviews the sequential hy- drolysis of ATPADPAMPadenosine catalyzed by these ecto-enzymes from different trypanosomatids. These reactions participate in the salvage of purines in these parasites and simultaneously interfere with the establishment of in- fection and changes in the host immune response.
{"title":"Ecto-Nucleoside Triphosphate Diphosphohydrolase Activities in Trypanosomatids:Possible Roles in Infection, Virulence and Purine Recycling","authors":"J. Meyer‐Fernandes, D. Cosentino-Gomes, Danielle P. Vieira, A. Lopes","doi":"10.2174/1874421401004010116","DOIUrl":"https://doi.org/10.2174/1874421401004010116","url":null,"abstract":"Ecto-nucleoside triphosphate diphosphohydrolases (ecto-NTPDases), also known as ecto-ATPases and/or ecto- apyrases, are integral membrane glycoproteins or soluble enzymes that are dependent on divalent cations. These ecto- enzymes are important ecto-nucleotidases that are characterized by the ability to hydrolyze nucleoside triphosphates and nucleoside diphosphates to the monophosphate form. The hydrolysis of nucleoside monophosphates to nucleosides such as adenosine may then be catalyzed by the action of ecto-5´nucleotidases. The present study reviews the sequential hy- drolysis of ATPADPAMPadenosine catalyzed by these ecto-enzymes from different trypanosomatids. These reactions participate in the salvage of purines in these parasites and simultaneously interfere with the establishment of in- fection and changes in the host immune response.","PeriodicalId":89294,"journal":{"name":"The open parasitology journal","volume":"1 1","pages":"116-119"},"PeriodicalIF":0.0,"publicationDate":"2010-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89780755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-12-10DOI: 10.2174/1874421401004010139
M. Motta, M. Cristina
Some trypanosomatids harbor a symbiotic bacterium, which maintains a close association with the host, consti- tuting an excellent model to study organelle origin and cellular evolution. Molecular data show that all endosymbiont- harboring trypanosomatids are grouped together in a single phylogenetic branch. According to rRNA sequences, symbi- onts of different species are similar, being classified in the s division of Proteobacteria, thus suggesting that a single evo- lutionary event gave rise to the symbiosis in the Trypanosomatidae family. The bacterium is enclosed by two unit mem- branes and presents a reduced peptidoglycan layer, which is essential for cell division and morphological maintenance. Regarding the protein composition, the number of intramembrane particles in the endosymbiont envelope is similar to that described for Gram-negative bacteria. Lipid analyses of purified endosymbionts show absence of sterols and indicate phosphatidylcholine as a major component of the envelope, as described in other intracellular bacteria. The presence of the endosymbiont is associated with distinct ultrastructural and physico-chemical alterations in the trypanosomatid and in- fluences the protozoan interaction with the insect host and mammalian cells. Symbiont-containing trypanosomatids are able to infect and to replicate inside fibroblasts and macrophages, whose microbicidal activity was deactivated by HIV-1 infection. The symbiosis in trypanosomatids is characterized by intensive metabolic exchanges; the bacterium expresses enzymes and metabolic precursors that complete essential biosynthetic pathways of the protozoan. Conversely, the sym- biont is capable of obtaining part of the required energetic molecules from the host glycosomes. Taken together data sug- gest that endosymbiosis in trypanosomatids represents an interesting model to study cell evolution.
{"title":"Endosymbiosis in Trypanosomatids as a Model to Study Cell Evolution","authors":"M. Motta, M. Cristina","doi":"10.2174/1874421401004010139","DOIUrl":"https://doi.org/10.2174/1874421401004010139","url":null,"abstract":"Some trypanosomatids harbor a symbiotic bacterium, which maintains a close association with the host, consti- tuting an excellent model to study organelle origin and cellular evolution. Molecular data show that all endosymbiont- harboring trypanosomatids are grouped together in a single phylogenetic branch. According to rRNA sequences, symbi- onts of different species are similar, being classified in the s division of Proteobacteria, thus suggesting that a single evo- lutionary event gave rise to the symbiosis in the Trypanosomatidae family. The bacterium is enclosed by two unit mem- branes and presents a reduced peptidoglycan layer, which is essential for cell division and morphological maintenance. Regarding the protein composition, the number of intramembrane particles in the endosymbiont envelope is similar to that described for Gram-negative bacteria. Lipid analyses of purified endosymbionts show absence of sterols and indicate phosphatidylcholine as a major component of the envelope, as described in other intracellular bacteria. The presence of the endosymbiont is associated with distinct ultrastructural and physico-chemical alterations in the trypanosomatid and in- fluences the protozoan interaction with the insect host and mammalian cells. Symbiont-containing trypanosomatids are able to infect and to replicate inside fibroblasts and macrophages, whose microbicidal activity was deactivated by HIV-1 infection. The symbiosis in trypanosomatids is characterized by intensive metabolic exchanges; the bacterium expresses enzymes and metabolic precursors that complete essential biosynthetic pathways of the protozoan. Conversely, the sym- biont is capable of obtaining part of the required energetic molecules from the host glycosomes. Taken together data sug- gest that endosymbiosis in trypanosomatids represents an interesting model to study cell evolution.","PeriodicalId":89294,"journal":{"name":"The open parasitology journal","volume":"52 1","pages":"139-147"},"PeriodicalIF":0.0,"publicationDate":"2010-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90843488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-12-10DOI: 10.2174/1874421401004010132
A. Lima, J. Mottram
Trypanosomatids rely on peptidases as potent virulence factors and were recently found to contain a unique set of natural peptidase inhibitors not found in higher eukaryotes or in yeast, but present in a limited number of bacteria. Cha- gasin, identified in Trypanosoma cruzi, is a tight-binding, high affinity inhibitor of papain-like cysteine peptidases that has an Ig-like fold and inactivates target enzymes through a limited number of contacts mediated by a few conserved residues on three exposed loops. Chagasin homologues in other protozoa and bacteria are mostly single genes named ICPs, and to- gether with chagasin compose family I42 at MEROPS, the peptidase and peptidase inhibitors database (http://merops.sanger.ac.uk/). The biological function of chagasin/ICPs seems to vary depending on the organism, but generally, the current studies point to a role in controlling the activity of endogenous parasite CPs, influencing parasite differentiation, virulence and different aspects of the host response to infection. More recently, natural inhibitors of serine peptidases that share similarity to bacterial ecotins were identified in trypanosomatids and named ISPs. Ecotins are spe- cific to trypsin-fold serine peptidases, enzymes which are not present in trypanosomatids. ISPs are limited to Trypano- somes and Leishmania and to date, only ISP2 proven to have an inhibitory function. In Leishmania, ISP2 seems to control the activity of host SPs at the initial stages of infection in order to ensure subsequent parasite survival in macrophages. The main aspects of chagasin/ICP biochemistry, structure and biological function and the recent findings on ISPs will be covered in this review.
{"title":"Trypanosomatid-Encoded Inhibitors of Peptidases: Unique Structural Features and Possible Roles as Virulence Factors","authors":"A. Lima, J. Mottram","doi":"10.2174/1874421401004010132","DOIUrl":"https://doi.org/10.2174/1874421401004010132","url":null,"abstract":"Trypanosomatids rely on peptidases as potent virulence factors and were recently found to contain a unique set of natural peptidase inhibitors not found in higher eukaryotes or in yeast, but present in a limited number of bacteria. Cha- gasin, identified in Trypanosoma cruzi, is a tight-binding, high affinity inhibitor of papain-like cysteine peptidases that has an Ig-like fold and inactivates target enzymes through a limited number of contacts mediated by a few conserved residues on three exposed loops. Chagasin homologues in other protozoa and bacteria are mostly single genes named ICPs, and to- gether with chagasin compose family I42 at MEROPS, the peptidase and peptidase inhibitors database (http://merops.sanger.ac.uk/). The biological function of chagasin/ICPs seems to vary depending on the organism, but generally, the current studies point to a role in controlling the activity of endogenous parasite CPs, influencing parasite differentiation, virulence and different aspects of the host response to infection. More recently, natural inhibitors of serine peptidases that share similarity to bacterial ecotins were identified in trypanosomatids and named ISPs. Ecotins are spe- cific to trypsin-fold serine peptidases, enzymes which are not present in trypanosomatids. ISPs are limited to Trypano- somes and Leishmania and to date, only ISP2 proven to have an inhibitory function. In Leishmania, ISP2 seems to control the activity of host SPs at the initial stages of infection in order to ensure subsequent parasite survival in macrophages. The main aspects of chagasin/ICP biochemistry, structure and biological function and the recent findings on ISPs will be covered in this review.","PeriodicalId":89294,"journal":{"name":"The open parasitology journal","volume":"80 1","pages":"132-138"},"PeriodicalIF":0.0,"publicationDate":"2010-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85023052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-12-10DOI: 10.2174/1874421401004010077
M. Alves, W. Colli
Members of the Gp85/trans-sialidase (Gp85/TS) superfamily and mucins play an essential role in the invasion of host cells by T. cruzi trypomastigotes. Together, they constitute a large portion of the genome; approximately 700 and 433 genes encode Gp85/TS glycoproteins and mucins (as do a similar amount of pseudogenes), respectively. Gp85/TS proteins bind to a variety of host cell receptors and extracellular matrix components and binding of TS to host cells is in- dependent of their enzymatic activity. Because mucins are the main substrate for TS, their interaction with host cells has been described as carbohydrate-dependent. Complex signaling cascades operate during the infection process within both parasite and host cells, but most research into signaling events has been limited to those of host cells. Much less informa- tion about the parasitic side is available; these pathways will be the subjects of intense research in the near future. Analy- ses of protein kinases and phosphatases in the parasite genome show pathways common to other organisms, but also para- site-specific pathways that should be exploited as candidates for drug targeting.
{"title":"Signaling Pathways in Trypanosoma cruzi that Modulate Host Cell Interaction","authors":"M. Alves, W. Colli","doi":"10.2174/1874421401004010077","DOIUrl":"https://doi.org/10.2174/1874421401004010077","url":null,"abstract":"Members of the Gp85/trans-sialidase (Gp85/TS) superfamily and mucins play an essential role in the invasion of host cells by T. cruzi trypomastigotes. Together, they constitute a large portion of the genome; approximately 700 and 433 genes encode Gp85/TS glycoproteins and mucins (as do a similar amount of pseudogenes), respectively. Gp85/TS proteins bind to a variety of host cell receptors and extracellular matrix components and binding of TS to host cells is in- dependent of their enzymatic activity. Because mucins are the main substrate for TS, their interaction with host cells has been described as carbohydrate-dependent. Complex signaling cascades operate during the infection process within both parasite and host cells, but most research into signaling events has been limited to those of host cells. Much less informa- tion about the parasitic side is available; these pathways will be the subjects of intense research in the near future. Analy- ses of protein kinases and phosphatases in the parasite genome show pathways common to other organisms, but also para- site-specific pathways that should be exploited as candidates for drug targeting.","PeriodicalId":89294,"journal":{"name":"The open parasitology journal","volume":"16 1","pages":"77-83"},"PeriodicalIF":0.0,"publicationDate":"2010-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89431852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-08-09DOI: 10.2174/1874421401004010024
I. Vokřál, V. Křížová, J. Lamka, V. Kubíček, B. Szotáková, M. Várady, M. Nobilis, L. Skálová
The aim of present project was to find out if in vivo contact of Haemonchus contortus with benzimidazole anthelmintic flubendazole (FLU) during treatment of its hosts (sheep) with low doses of FLU affects helminths’ drugmetabolizing enzyme activities. Four groups of lambs, experimentally infected with H. contortus, were treated three-times orally with 0.0, 0.25, 0.50 or 1.00 mg per kg of body weight of FLU in three consecutive days. Twenty four hours after the last FLU dose, the nematodes were isolated, homogenized and subcellular fractions were prepared. In these subcellular fractions, biotransformation of FLU and the activities of carbonyl reducing enzymes and conjugation enzymes were assayed. The results showed that H. contortus enzymes were able to conjugate p-nitrophenol with glucose but not with glucuronic acid. The exposure of H.contortus to FLU (the highest FLU dose) caused a significant increase in activities of FLU reductases, D,L-glyceraldehyde reductases and glutathion S-transferases.
{"title":"Effect of Flubendazole on Biotransformation Enzymes Activities in Haemonchus contortus~!2010-03-18~!2010-06-16~!2010-08-07~!","authors":"I. Vokřál, V. Křížová, J. Lamka, V. Kubíček, B. Szotáková, M. Várady, M. Nobilis, L. Skálová","doi":"10.2174/1874421401004010024","DOIUrl":"https://doi.org/10.2174/1874421401004010024","url":null,"abstract":"The aim of present project was to find out if in vivo contact of Haemonchus contortus with benzimidazole anthelmintic flubendazole (FLU) during treatment of its hosts (sheep) with low doses of FLU affects helminths’ drugmetabolizing enzyme activities. Four groups of lambs, experimentally infected with H. contortus, were treated three-times orally with 0.0, 0.25, 0.50 or 1.00 mg per kg of body weight of FLU in three consecutive days. Twenty four hours after the last FLU dose, the nematodes were isolated, homogenized and subcellular fractions were prepared. In these subcellular fractions, biotransformation of FLU and the activities of carbonyl reducing enzymes and conjugation enzymes were assayed. The results showed that H. contortus enzymes were able to conjugate p-nitrophenol with glucose but not with glucuronic acid. The exposure of H.contortus to FLU (the highest FLU dose) caused a significant increase in activities of FLU reductases, D,L-glyceraldehyde reductases and glutathion S-transferases.","PeriodicalId":89294,"journal":{"name":"The open parasitology journal","volume":"140 1","pages":"24-28"},"PeriodicalIF":0.0,"publicationDate":"2010-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78493844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-03-18DOI: 10.2174/1874421401004010005
Alane Beatriz Vermelho, M. Branquinha, C. M. d'Avila-Levy, A. L. Santos, Edilma Paraguai de Souza Dias, A. C. Melo
In this review, we report the recent developments in the characterization of peptidases and their possible biological functions in the Trypanosomatidae family. The focus will be on peptidases from Trypanosoma cruzi, Leishmania spp., African trypanosomes and plant and insect trypanosomatids. There are numerous events in parasite development where the involvement of peptidases has been established, and they will be approached in the present review. Also in this review we will discuss the central roles have been proposed for peptidases in diverse processes such as virulence, host cell interaction and invasion, catabolism of host proteins, differentiation, cell cycle progression and both stimulation and evasion of host immune responses.
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