Arginine kinase of the flagellate protozoa <i>Trypanosoma cruzi</i>

Alonso, Guillermo D.; Pereira, Claudio A.; Remedi, Marı́a S.; Paveto, Maria Cristina; Cochella, Luisa; Ivaldi, Marc; Burgos, Nelia M. Gerez de; Torres, Héctor N.; Flawiá, Mirtha M.

doi:10.1016/s0014-5793(01)02473-5

Cited by 53 publications

(24 citation statements)

References 20 publications

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“…Our results show that this gene is significantly up-regulated in epimastigotes and trypomastigotes; and this might reflect the fact that amastigotes have a constant supply of glucose and amino acids and therefore do not need such energy storage. Another explanation is that arginine kinase activity was not directly correlated with mRNA levels, a result already shown for epimastigotes (Alonso et al, 2001). …”

Section: Resultsmentioning

confidence: 84%

“…This reaction generates phosphoarginine, which serves as an ATP, and phosphate reservoir and supports burst of cellular activity during the life cycle (Alonso et al, 2001). Our results show that this gene is significantly up-regulated in epimastigotes and trypomastigotes; and this might reflect the fact that amastigotes have a constant supply of glucose and amino acids and therefore do not need such energy storage.…”

Section: Resultsmentioning

confidence: 99%

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Transcriptomic analysis reveals metabolic switches and surface remodeling as key processes for stage transition inTrypanosoma cruzi

Berná

Chiribao

Greif

et al. 2017

PeerJ

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American trypanosomiasis is a chronic and endemic disease which affects millions of people. Trypanosoma cruzi, its causative agent, has a life cycle that involves complex morphological and functional transitions, as well as a variety of environmental conditions. This requires a tight regulation of gene expression, which is achieved mainly by post-transcriptional regulation. In this work we conducted an RNAseq analysis of the three major life cycle stages of T. cruzi: amastigotes, epimastigotes and trypomastigotes. This analysis allowed us to delineate specific transcriptomic profiling for each stage, and also to identify those biological processes of major relevance in each state. Stage specific expression profiling evidenced the plasticity of T. cruzi to adapt quickly to different conditions, with particular focus on membrane remodeling and metabolic shifts along the life cycle. Epimastigotes, which replicate in the gut of insect vectors, showed higher expression of genes related to energy metabolism, mainly Krebs cycle, respiratory chain and oxidative phosphorylation related genes, and anabolism related genes associated to nucleotide and steroid biosynthesis; also, a general down-regulation of surface glycoprotein coding genes was seen at this stage. Trypomastigotes, living extracellularly in the bloodstream of mammals, express a plethora of surface proteins and signaling genes involved in invasion and evasion of immune response. Amastigotes mostly express membrane transporters and genes involved in regulation of cell cycle, and also express a specific subset of surface glycoprotein coding genes. In addition, these results allowed us to improve the annotation of the Dm28c genome, identifying new ORFs and set the stage for construction of networks of co-expression, which can give clues about coded proteins of unknown functions.

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Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Transcriptomic analysis reveals metabolic switches and surface remodeling as key processes for stage transition inTrypanosoma cruzi

Berná

Chiribao

Greif

et al. 2017

PeerJ

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“…Multiple evidence indicates that T. cruzi arginine kinase is strongly regulated by intra and extracellular conditions: (1) the arginine kinase protein and the associated specific activity increase continuously along the epimastigote growth curve, suggesting a correlation between the enzyme activity and the nutrient availability or parasite density [83]; (2) the existence of a relationship between the arginine transport rate, arginine kinase activity and the parasite stage and replication capability was recently described, indicating a critical role of arginine kinase as a regulator of energetic reserves and cell growth [58]; and (3) the homologous overexpression of T. cruzi arginine kinase improves the ability of the transfectant cells to grow and resist to nutritional and pH stress conditions [84]. Arginine kinase would play a role as a stress resistance factor when expressed in organisms that lack this enzyme, such as yeast and bacteria.…”

Section: Arginine Metabolismmentioning

confidence: 99%

Amino Acid Metabolic Routes in Trypanosoma cruzi: Possible Therapeutic Targets Against Chagas; Disease

Silber

Colli²,

Ulrich³

et al. 2005

CDTID

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Chagas' disease is a zoonosis caused by the parasite Trypanosoma cruzi, a haematic protozoan, transmitted by insects from the Reduviidae family. This constitutes a relevant health and socio-economic problem in the Americas, with 11 - 18 million people infected, and approximately 100 million people at risk. The therapeutic possibilities rely into two drugs, nifurtimox and benznidazole, that were discovered more than thirty years ago, and are mainly successful during the acute phase of the disease. In the majority of the cases the disease is diagnosed in the chronic phase, when the therapy is inefficient and the probability of cure is low. In addition, these drugs are highly toxic, with systemic side effects on patients. Trypanosoma cruzi has a metabolism largely based on the consumption of amino acids, mainly proline, aspartate and glutamate, which constitute the main carbon and energy sources in the insect stage of the parasite life cycle. These amino acids also participate in the differentiation process of the replicative non-infective form (epimastigote) to the non-replicative infective form (trypomastigote). In particular, the participation of proline in the intracellular differentiation cycle, which occurs in the mammalian host, was recently demonstrated. In addition, an arginine kinase has been described in T. cruzi and T. brucei, which converts free arginine to phosphoarginine, a phosphagen with a role as an energy reservoir. Arginine kinase seems to be an essential component of energy management during stress conditions. Taken together, these data indicate that amino acid metabolism may provide multiple as yet unexplored targets for therapeutic drugs.

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“…There is an evident relationship between the activity of guanidino kinases and the energy requirements within the cell. In T. cruzi, in particular, it has been suggested that the action of arginine quinase acquires primary importance during the invertebrate phase of the life cycle where, due to variations in insect feeding status, the nutrient supply is not as constant as in the human host [51,52]. Thus, phosphoarginine is a rapid source of energy either during bursts of cellular activity or under starvation stress conditions.…”

Section: Arginine Quinasementioning

confidence: 99%

The Chemotherapy of Chagas Disease: An Overview

Paulino

Iribarne²,

Dubin³

et al. 2005

MRMC

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The review presents: a) a brief description of the disease; b) a summary of the most important metabolic targets so far identified in Trypanosome cruzi (T. cruzi) along with corresponding inhibitor compounds; c) the current state of knowledge on the trypanothione reductase system of trypanosomatids with reference to oxidative stress defenses; d) detailed discussions on T. cruzi trypanothione reductase inhibitors such as nitrofuranes, naphthoquinones and phenothiazines. As yet, the chemotherapy of Chagas' disease remains an unsolved problem. Further search for new drugs must continue by means of nucleating existing chemotherapy efforts.

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Arginine kinase of the flagellate protozoa Trypanosoma cruzi

Cited by 53 publications

References 20 publications

Transcriptomic analysis reveals metabolic switches and surface remodeling as key processes for stage transition inTrypanosoma cruzi

Transcriptomic analysis reveals metabolic switches and surface remodeling as key processes for stage transition inTrypanosoma cruzi

Amino Acid Metabolic Routes in Trypanosoma cruzi: Possible Therapeutic Targets Against Chagas; Disease

The Chemotherapy of Chagas Disease: An Overview

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