All living organisms are destined to die. Cells, the core of those living creatures, move toward the irresistible direction of death. The question of how to die is critical and is very interesting. There are various types of death in life, including natural death, accidental death, questionable death, suicide, and homicide. The mechanisms and molecules involved in cell death also differ depending on the type of death. The dysenteric amoeba, E. histolytica, designated by the German zoologist Fritz Schaudinn in 1903, has the meaning of tissue lysis; i.e., tissue destroying, in its name. It was initially thought that the amoebae lyse tissue very quickly leading to cell death called necrosis. However, advances in measuring cell death have allowed us to more clearly investigate the various forms of cell death induced by amoeba. Increasing evidence has shown that E. histolytica can cause host cell death through induction of various intracellular signaling pathways. Understanding of the mechanisms and signaling molecules involved in host cell death induced by amoeba can provide new insights on the tissue pathology and parasitism in human amoebiasis. In this review, we emphasized on the signaling role of NADPH oxidases in reactive oxygen species (ROS)-dependent cell death by pathogenic E. histolytica.
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The pathogenic free-living amoeba Naegleria fowleri causes primary amoebic meningoencephalitis, a fatal infection, by penetrating the nasal mucosa and migrating to the brain via the olfactory nerves. N. fowleri can induce host cell death via lytic necrosis. Similar to phosphorylation, O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation) is involved in various cell-signaling processes, including apoptosis and proliferation, with O-GlcNAc addition and removal regulated by O-GlcNAc transferase and O-GlcNAcase (OGA), respectively. However, the detailed mechanism of host cell death induced by N. fowleri is unknown. In this study, we investigated whether N. fowleri can induce the modulation of O-GlcNAcylated proteins during cell death in Jurkat T cells. Co-incubation with live N. fowleri trophozoites increased DNA fragmentation. In addition, incubation with N. fowleri induced a dramatic reduction in O-GlcNAcylated protein levels in 30 min. Moreover, pretreatment of Jurkat T cells with the OGA inhibitor PUGNAc prevented N. fowleri–induced O-deGlcNAcylation and DNA fragmentation. These results suggest that O-deGlcNAcylation is an important signaling process that occurs during Jurkat T cell death induced by N. fowleri.
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The enteric protozoan parasite Entamoeba histolytica is the causative agent of human amebiasis. During infection, adherence of E. histolytica through Gal/GalNAc lectin on the surface of the amoeba can induce caspase-3-dependent or -independent host cell death. Phosphorylinositol 3-kinase (PI3K) and protein kinase C (PKC) in E. histolytica play an important function in the adhesion, killing, or phagocytosis of target cells. In this study, we examined the role of amoebic PI3K and PKC in amoeba-induced apoptotic cell death in Jurkat T cells. When Jurkat T cells were incubated with E. histolytica trophozoites, phosphatidylserine (PS) externalization and DNA fragmentation in Jurkat cells were markedly increased compared to those of cells incubated with medium alone. However, when amoebae were pretreated with a PI3K inhibitor, wortmannin before being incubated with E. histolytica, E. histolytica-induced PS externalization and DNA fragmentation in Jurkat cells were significantly reduced compared to results for amoebae pretreated with DMSO. In addition, pretreatment of amoebae with a PKC inhibitor, staurosporine strongly inhibited Jurkat T cell death. However, E. histolytica-induced cleavage of caspase-3, -6, and -7 were not inhibited by pretreatment of amoebae with wortmannin or staurosporin. In addition, we found that amoebic PI3K and PKC have an important role on amoeba adhesion to host compartment. These results suggest that amebic PI3K and PKC activation may play an important role in caspase-independent cell death in Entamoeba-induced apoptosis.
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Entamoeba histolytica, which causes amoebic colitis and occasionally liver abscess in humans, is able to induce host cell death. However, signaling mechanisms of colon cell death induced by E. histolytica are not fully elucidated. In this study, we investigated the signaling role of NOX in cell death of HT29 colonic epithelial cells induced by E. histolytica. Incubation of HT29 cells with amoebic trophozoites resulted in DNA fragmentation that is a hallmark of apoptotic cell death. In addition, E. histolytica generate intracellular reactive oxygen species (ROS) in a contact-dependent manner. Inhibition of intracellular ROS level with treatment with DPI, an inhibitor of NADPH oxidases (NOXs), decreased Entamoeba-induced ROS generation and cell death in HT29 cells. However, pan-caspase inhibitor did not affect E. histolytica-induced HT29 cell death. In HT29 cells, catalytic subunit NOX1 and regulatory subunit Rac1 for NOX1 activation were highly expressed. We next investigated whether NADPH oxidase 1 (NOX1)-derived ROS is closely associated with HT29 cell death induced by E. histolytica. Suppression of Rac1 by siRNA significantly inhibited Entamoeba-induced cell death. Moreover, knockdown of NOX1 by siRNA, effectively inhibited E. histolytica-triggered DNA fragmentation in HT29 cells. These results suggest that NOX1-derived ROS is required for apoptotic cell death in HT29 colon epithelial cells induced by E. histolytica.
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Involvement of NOX2-derived ROS in human hepatoma HepG2 cell death induced by Entamoeba histolytica Young Ah Lee, Myeong Heon Shin Parasites, Hosts and Diseases.2023; 61(4): 388. CrossRef
Signaling Role of NADPH Oxidases in ROS-Dependent Host Cell Death Induced by Pathogenic Entamoeba histolytica Young Ah Lee, Seobo Sim, Kyeong Ah Kim, Myeong Heon Shin The Korean Journal of Parasitology.2022; 60(3): 155. CrossRef
The interaction betweenEntamoeba histolyticaand enterobacteria shed light on an ancient antibacterial response Nancy Guillén Cellular Microbiology.2019;[Epub] CrossRef
NOX4 activation is involved in ROS‐dependent Jurkat T‐cell death induced by Entamoeba histolytica Young Ah Lee, Kyeong Ah Kim, Arim Min, Myeong Heon Shin Parasite Immunology.2019;[Epub] CrossRef
O-deGlcNAcylation is required for Entamoeba histolytica-induced HepG2 cell death Young Ah Lee, Arim Min, Myeong Heon Shin Microbial Pathogenesis.2018; 123: 285. CrossRef
GOLPH3 expression promotes the resistance of HT29 cells to 5‑fluorouracil by activating multiple signaling pathways Ming‑Zhen Wang, Cheng‑Zhi Qiu, Wai‑Shi Yu, Yan‑Ta Guo, Chun‑Xiao Wang, Zhi‑Xiong Chen Molecular Medicine Reports.2017;[Epub] CrossRef
Infection Strategies of Intestinal Parasite Pathogens and Host Cell Responses Bruno M. Di Genova, Renata R. Tonelli Frontiers in Microbiology.2016;[Epub] CrossRef
A whole-genome RNAi screen uncovers a novel role for human potassium channels in cell killing by the parasite Entamoeba histolytica Chelsea Marie, Hans P. Verkerke, Dan Theodorescu, William A. Petri Scientific Reports.2015;[Epub] CrossRef
Degradation of the Transcription Factors NF-κB, STAT3, and STAT5 Is Involved in Entamoeba histolytica-Induced Cell Death in Caco-2 Colonic Epithelial Cells Kyeong Ah Kim, Arim Min, Young Ah Lee, Myeong Heon Shin The Korean Journal of Parasitology.2014; 52(5): 459. CrossRef
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The EhCPADH112 Complex of Entamoeba histolytica Interacts with Tight Junction Proteins Occludin and Claudin-1 to Produce Epithelial Damage Abigail Betanzos, Rosario Javier-Reyna, Guillermina García-Rivera, Cecilia Bañuelos, Lorenza González-Mariscal, Michael Schnoor, Esther Orozco, Johanna M. Brandner PLoS ONE.2013; 8(6): e65100. CrossRef
Entamoeba histolytica is an enteric tissue-invading protozoan parasite that can cause amebic colitis and liver abscess in humans. E. histolytica has the capability to kill colon epithelial cells in vitro; however, information regarding the role of calpain in colon cell death induced by ameba is limited. In this study, we investigated whether calpains are involved in the E. histolytica-induced cell death of HT-29 colonic epithelial cells. When HT-29 cells were co-incubated with E. histolytica, the propidium iodide stained dead cells markedly increased compared to that in HT-29 cells incubated with medium alone. This pro-death effect induced by ameba was effectively blocked by pretreatment of HT-29 cells with the calpain inhibitor, calpeptin. Moreover, knockdown of m- and ?-calpain by siRNA significantly reduced E. histolytica-induced HT-29 cell death. These results suggest that m- and ?-calpain may be involved in colon epithelial cell death induced by E. histolytica.
Citations
Citations to this article as recorded by
Involvement of NOX2-derived ROS in human hepatoma HepG2 cell death induced by Entamoeba histolytica Young Ah Lee, Myeong Heon Shin Parasites, Hosts and Diseases.2023; 61(4): 388. CrossRef
Signaling Role of NADPH Oxidases in ROS-Dependent Host Cell Death Induced by Pathogenic Entamoeba histolytica Young Ah Lee, Seobo Sim, Kyeong Ah Kim, Myeong Heon Shin The Korean Journal of Parasitology.2022; 60(3): 155. CrossRef
Infection Strategies of Intestinal Parasite Pathogens and Host Cell Responses Bruno M. Di Genova, Renata R. Tonelli Frontiers in Microbiology.2016;[Epub] CrossRef
Degradation of the Transcription Factors NF-κB, STAT3, and STAT5 Is Involved in Entamoeba histolytica-Induced Cell Death in Caco-2 Colonic Epithelial Cells Kyeong Ah Kim, Arim Min, Young Ah Lee, Myeong Heon Shin The Korean Journal of Parasitology.2014; 52(5): 459. CrossRef
Entamoeba histolytica Induces Cell Death of HT29 Colonic Epithelial Cells via NOX1-Derived ROS Kyeong Ah Kim, Ju Young Kim, Young Ah Lee, Arim Min, Young Yil Bahk, Myeong Heon Shin The Korean Journal of Parasitology.2013; 51(1): 61. CrossRef
Mechanisms of Adherence, Cytotoxicity and Phagocytosis Modulate the Pathogenesis of
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Nathaniel CV Christy, William A Petri Future Microbiology.2011; 6(12): 1501. CrossRef
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