Effect of calcium antagonists, calcium channel blockers and calmodulin inhibitors on the growth and encystation of Entamoeba histolytica and E. invadens

Makioka, Asao; Kumagai, Masahiro; Ohtomo, Hiroshi; Kobayashi, Seiki; Takeuchi, Tsutomu

doi:10.1007/s004360100453

Cited by 26 publications

(9 citation statements)

References 17 publications

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“…Two purine analogs, cladribine and fludarabine, showed 79% and 77% inhibition at 5 µM, respectively, but are not promising for further development because of reported adverse effects on patients. Trifluoperazine, a compound with known amebicidal activity 10 was also identified as a primary hit, confirming the sensitivity of our whole cell HTS assay format.…”

supporting

confidence: 69%

A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target

Debnath

Parsonage

Andrade

et al. 2012

Nat Med

283

310

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supporting

confidence: 69%

A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target

Debnath

Parsonage

Andrade

et al. 2012

Nat Med

283

310

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“…Calcium is also important in numerous cellular processes in E . histolytica , such as development and virulence [ 62 , 63 ]. Five putative Ca 2+ -ATPases, which could be important in the regulation of the cytoplasmic calcium concentration, have been recently identified in E .…”

Section: Discussionmentioning

confidence: 99%

Proteomic Identification of Oxidized Proteins in Entamoeba histolytica by Resin-Assisted Capture: Insights into the Role of Arginase in Resistance to Oxidative Stress

et al. 2016

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Entamoeba histolytica is an obligate protozoan parasite of humans, and amebiasis, an infectious disease which targets the intestine and/or liver, is the second most common cause of human death due to a protozoan after malaria. Although amebiasis is usually asymptomatic, E. histolytica has potent pathogenic potential. During host infection, the parasite is exposed to reactive oxygen species that are produced and released by cells of the innate immune system at the site of infection. The ability of the parasite to survive oxidative stress (OS) is essential for a successful invasion of the host. Although the effects of OS on the regulation of gene expression in E. histolytica and the characterization of some proteins whose function in the parasite's defense against OS have been previously studied, our knowledge of oxidized proteins in E. histolytica is lacking. In order to fill this knowledge gap, we performed a large-scale identification and quantification of the oxidized proteins in oxidatively stressed E. histolytica trophozoites using resin-assisted capture coupled to mass spectrometry. We detected 154 oxidized proteins (OXs) and the functions of some of these proteins were associated with antioxidant activity, maintaining the parasite's cytoskeleton, translation, catalysis, and transport. We also found that oxidation of the Gal/GalNAc impairs its function and contributes to the inhibition of E. histolytica adherence to host cells. We also provide evidence that arginase, an enzyme which converts L-arginine into L-ornithine and urea, is involved in the protection of the parasite against OS. Collectively, these results emphasize the importance of OS as a critical regulator of E. histolytica's functions and indicate a new role for arginase in E. histolytica's resistance to OS.

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“…Among the numerous calpain isoforms, m- and µ-calpain (conventional calpains) are ubiquitously expressed and are regulated by micromolar and millimolar increases in intracellular Ca 2+ levels, respectively [9]. They are also the most extensively analyzed calpain isoforms and have been shown to play roles in various physiological functions, including cell motility [10], migration [11] apoptosis [12,13], cell growth [14], and cell cycle progression [15].…”

mentioning

confidence: 99%

“…To address the role of calpain activity in E. histolytica -induced HT-29 cell death, we designed siRNA to selectively knockdown the expressions of calpains. Because the 2 ubiquitous calpain isoforms, m- and µ-calpain, are functional only when associated with a small common regulatory subunit [9], we transfected host cells with specific siRNA to specifically knockdown either m- or µ-calpain, knockdown respectively. Preliminary experiments with siRNA were performed to determine optimum dose and incubation time by examining siRNA concentrations of 20, 40, 80, or 160 nM for 24, 48, or 72 hr.…”

mentioning

confidence: 99%

Calpains are Involved inEntamoeba histolytica-Induced Death of HT-29 Colonic Epithelial Cells

et al. 2011

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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 µ-calpain by siRNA significantly reduced E. histolytica-induced HT-29 cell death. These results suggest that m- and µ-calpain may be involved in colon epithelial cell death induced by E. histolytica.

show abstract

Effect of calcium antagonists, calcium channel blockers and calmodulin inhibitors on the growth and encystation of Entamoeba histolytica and E. invadens

Cited by 26 publications

References 17 publications

A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target

A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target

Proteomic Identification of Oxidized Proteins in Entamoeba histolytica by Resin-Assisted Capture: Insights into the Role of Arginase in Resistance to Oxidative Stress

Calpains are Involved inEntamoeba histolytica-Induced Death of HT-29 Colonic Epithelial Cells

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