Entamoeba histolytica: Differential gene expression during programmed cell death and identification of early pro- and anti-apoptotic signals

Monroy, Virginia Sánchez; Flores, M; Villalba-Magdaleno, José D Artagnan; García, Consuelo Gómez; Ishiwara, D. Guillermo Pérez

doi:10.1016/j.exppara.2010.05.027

Cited by 13 publications

(7 citation statements)

References 69 publications

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“…Moreover, we also identified some transcriptomic changes that are often observed in the intracellular calcium imbalance such as cytoskeleton rearrangement and vesicular traffic, reinforcing the notion that the trophozoites were exposed to ER stress in peritoneal implantation. This observation agrees well with our previous reports in which the triggers that induce PCD in vitro concomitantly caused calcium release from the ER, increasing intracellular calcium concentrations, and increasing the expression and activity of some PCD-related proteins including calpain [12,25,14,26]. In another study, we modelled a hypothetical 3D structure of the E. histolytica calpain-like protein, based on the conserved domains previously identified in the primary sequence of the protein [26].…”

Section: Discussionsupporting

confidence: 91%

Transcriptome Analysis of Entamoeba histolytica Trophozoites during in vivo Contact-independent Mediated Host-parasite Interaction: Putative Pathways Related to PCD

Ishiwara

Shibayama²,

Nakada‐Tsukui³

et al. 2022

MRJI

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Aim: In the present study, we exploited DNA microarray-based transcriptome analysis and showed overall changes in gene expression in vivo of amoebic trophozoites that interact with animal soluble factors using an intraperitoneal dialysis bag model to elucidate putative molecular pathways and genes involved in this interaction. Study Design: We exploited DNA microarray-based transcriptome analysis. Results: An analysis from a network including the interactions of up-regulated genes and their neighbors revealed the presence of 11 functionally related modules. Six of the modules obtained were related to endoplasmic reticulum (ER) functions, such as degradation, stress, proteasome-ubiquitination, phosphorylation, lipid metabolism, and protein sorting. Furthermore, major transcriptional changes displayed by the parasite at the beginning of interaction were attributed to the response to the host defense. These data are consistent with the notion that the concerted expression of genes necessary for survival such as increment in protein synthesis, cytoskeleton rearrangement, vesicular traffic and genes involved in cell death including calcium imbalance and the ER signals associated with protein degradation (ERAD) is an overall landscape during the in vivo interaction between the amoebic trophozoites and animal soluble factors, and suggest that the ER stress is one of the main pathways leading to programmed cell death in E. histolytica. Conclusion: The present findings on the global transcriptional changes displayed by the parasite at the early stages of interaction with host environments in peritoneal implantation indicate that a substantial proportion of concerted changes in gene expression in amoebic trophozoites are attributable to the parasite’s response for cell death signals due to ER stress. A detailed knowledge of the underlying molecular mechanism might suggest the efficient elimination of this parasite by promoting their death pathways.

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Section: Discussionsupporting

confidence: 91%

Transcriptome Analysis of Entamoeba histolytica Trophozoites during in vivo Contact-independent Mediated Host-parasite Interaction: Putative Pathways Related to PCD

Ishiwara

Shibayama²,

Nakada‐Tsukui³

et al. 2022

MRJI

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“…We identified proteins that participate in endocytosis, such as vps36 and snf7, zinc binding proteins, as well as proteins that can bind calcium, including the grainins 1 and 2, which contain EF-hand calcium binding domains. Interestingly, previous studies have demonstrated an increase in the expression of grainins 1 and 2 at 30 min of PCD induction with G418, suggesting that these proteins could act as negative regulators of this event attempting to regulate the cytosolic concentration of free calcium related to the activation of PCD (Monroy et al, 2010 ).…”

Section: Discussionmentioning

confidence: 95%

A Calpain-Like Protein Is Involved in the Execution Phase of Programmed Cell Death of Entamoeba histolytica

Domínguez-Fernández

Rodríguez

Monroy

et al. 2018

Front. Cell. Infect. Microbiol.

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Oxygen or nitrogen oxidative species and chemical stress induce the programmed cell death (PCD) of Entamoeba histolytica trophozoites. PCD caused by the aminoglycoside G418 is reduced by incubation with the cysteine protease inhibitor E-64; however, no typical caspases or metacaspases have been detected in this parasite. Calpain, a cysteine protease activated by calcium, has been suggested to be part of a specific PCD pathway in this parasite because the specific calpain inhibitor Z-Leu-Leu-Leu-al diminishes the PCD of trophozoites. Here, we predicted the hypothetical 3D structure of a calpain-like protein of E. histolytica and produced specific antibodies against it. We detected the protein in the cytoplasm and near the nucleus. Its expression gradually increased during incubation with G418, with the highest level after 9 h of treatment. In addition, a specific calpain-like siRNA sequence reduced the cell death rate by 65%. All these results support the hypothesis that the calpain-like protein is one of the proteases involved in the execution phase of PCD in E. histolytica. The hypothetical interactome of the calpain-like protein suggests that it may activate or regulate other proteins that probably participate in PCD, including those with EF-hand domains or other calcium-binding sites.

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“…The sequences of both grainins contain at least one metal‐ligating EH‐hand motif, commonly seen in proteins that bind calcium. Both genes are upregulated in culture in response to inducers of programmed cell death (PCD), and a stress‐response role diminishing intracellular Ca 2+ was suggested (78), as was a role in calcium‐dependent endocytosis and granular exocytosis, aiding pathology (79). Lower levels of expression of both genes in mouse intestines, and of grainin 1 in ALA samples, were seen relative to in vitro cultures, possibly owing to higher stress levels in in vitro conditions (36,59).…”

Section: Introductionmentioning

confidence: 99%

Host–Parasite interactions in Entamoeba histolytica and Entamoeba dispar: what have we learned from their genomes?

Wilson

Weedall

Hall

2012

Parasite Immunology

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Invasive amoebiasis caused by Entamoeba histolytica is a major global health problem. Virulence is a rare outcome of infection, occurring in fewer than 1 in 10 infections. Not all strains of the parasite are equally virulent, and understanding the mechanisms and causes of virulence is an important goal of Entamoeba research. The sequencing of the genome of E. histolytica and the related avirulent species Entamoeba dispar has allowed whole-genome-scale analyses of genetic divergence and differential gene expression to be undertaken. These studies have helped elucidate mechanisms of virulence and identified genes differentially expressed in virulent and avirulent parasites. Here, we review the current status of the E. histolytica and E. dispar genomes and the findings of a number of genome-scale studies comparing parasites of different virulence.

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Entamoeba histolytica: Differential gene expression during programmed cell death and identification of early pro- and anti-apoptotic signals

Cited by 13 publications

References 69 publications

Transcriptome Analysis of Entamoeba histolytica Trophozoites during in vivo Contact-independent Mediated Host-parasite Interaction: Putative Pathways Related to PCD

Transcriptome Analysis of Entamoeba histolytica Trophozoites during in vivo Contact-independent Mediated Host-parasite Interaction: Putative Pathways Related to PCD

A Calpain-Like Protein Is Involved in the Execution Phase of Programmed Cell Death of Entamoeba histolytica

Host–Parasite interactions in Entamoeba histolytica and Entamoeba dispar: what have we learned from their genomes?

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