Molecular and biochemical characterization of calmodulin from Echinococcus granulosus

Wang, Ning; Zhong, Xianqiong; Song, Xingju; Gu, Xiaobin; Lai, Weiming; Xie, Yue; Peng, Xuerong; Yang, Guangyou

doi:10.1186/s13071-017-2545-2

Cited by 16 publications

(13 citation statements)

References 41 publications

(37 reference statements)

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“…have used Immunohistochemical localizations on different stages of the parasite, suggesting the expression of E. granulosus CaM (EgCaM) in the tegument tissues, protoscoleces parenchymal region, germinal layer as well as in the adult stage. The study showed physiologically active regions for EgCaM expression and suggested the crucial role of Ca2+ signaling pathway in the growth and development of the helminth and its function between E. granulosus and its host 9 .…”

Section: Introductionmentioning

confidence: 83%

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Calmodulin-specific small interfering RNA induces consistent expression suppression and morphological changes in Echinococcus granulosus

Mousavi

Afgar

Mohammadi

et al. 2019

Sci Rep

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Among parasitic helminths, biological features of Echinococcus granulosus have been a focus of particular interest in biology and medicine. The determinants and underlying molecular mechanisms of Echinococcus development in different host settings is largely unknown. The phenomenal bi-directional development of E. granulosus protoscoleces into multi-proglottid and/or microcysts, is a fascinating feature of the parasite cultivation. Calmodulin (CaM) is the major intracellular Ca2+ binding protein in plant and animal organisms. Many Ca 2+ -related processes in the physiology of eukaryotic organisms are CaM-dependent, however little is known on the role of CaM in platyhelminths growth and development. Small interfering (si) RNA-induced manipulations of the genes involving in the parasite development is an opportunity to explore novel approaches for cystic echinococcosis (CE) prevention and management. Regarding the fundamental role of CaM in cellular function of the parasites, in this study, we investigated the molecular and morphological changes induced by siRNA on CaM in different in vitro stages of E. granulosus . Three developmental stages of the tapeworm, protoscoleces, microcysts and strobilated worms, were cultivated in vitro in mono- and di-phasic media and three delivery methods, i.e. electroporation, soaking and electro-soaking, were used for RNA interference. The level of mRNA suppression as well as the phenotypic changes of the parasites were measured. Following RNA interference, EgCaM mRNA suppressions of 65–99% were recorded in different stages of the tapeworm as compared to untreated/unrelated siRNA controls. Lower viability, growth retardation, morphological abnormalities as well as EgCaM expression suppression were documented in the parasite implying potential of siRNA technology for the prevention and management of CE.

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Section: Introductionmentioning

confidence: 83%

“…Wang et al . showed EgCaM expression in the germinal layer and speculated that an unknown calcium-dependent mechanism occurs in this layer 9 . More in-depth investigations are needed on the probable role of CaM in the stability of the microcyst wall and germinal layer.…”

Section: Discussionmentioning

confidence: 99%

Calmodulin-specific small interfering RNA induces consistent expression suppression and morphological changes in Echinococcus granulosus

Mousavi

Afgar

Mohammadi

et al. 2019

Sci Rep

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“…Among the calmodulin-binding proteins, calcineurin has been found to be involved in apoptosis-related pathway initiation. Calmodulin was predicted as a potential drug target in E. multilocularis [54], and more recently identified and characterized in E. granulosus (Egcam) [56]. Egcam was shown to be expressed in the larva, germinal layer, and adult worm.…”

Section: Regulated Cell Death Of the Echinococcus Parasitementioning

confidence: 99%

Interactions between hydatid cyst and regulated cell death may provide new therapeutic opportunities

2019

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Cystic echinococcosis and alveolar echinococcosis are chronic zoonotic infections, transmitted throughout the world. Development of the cestode larval stages in the liver and lungs causes damage to intermediate hosts, including humans. Several pathways leading to the suppression of host immune response and the survival of the cysts in various hosts are known. Immune response modulation and regulated cell death (RCD) play a fundamental role in cyst formation, development and pathogenesis. RCD, referring to apoptosis, necrosis and autophagy, can be triggered either via intrinsic or extrinsic cell stimuli. In this review, we provide a general overview of current knowledge on the process of RCD during echinococcosis. The study of interactions between RCD and Echinococcus spp. metacestodes may provide in-depth understanding of echinococcosis pathogenesis and open new horizons for human intervention and treatment of the disease.

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“…The CaM gene is also expressed in the tegument tissue and parenchymal region of PSC [ 15 , 16 ]. In terms of evolution, CaM is one of the most ancient proteins in eukaryotes.…”

Section: Introductionmentioning

confidence: 99%

“…The functions of CaM include Ca 2+ binding and conversion of Ca 2+ signals through downstream proteins to regulate various physiological processes, such as muscle contraction, metabolism and cell motility [ 17 ]. Calcineurin and CaM have been linked to the regulation of the life cycle, development and cellular signaling activities, thus being potentially promising targets for the development of drugs that block the invasion of parasites and limit their growth [ 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

In vitro effects of tropisetron and granisetron against Echinococcus granulosus (s.s.) protoscoleces by involvement of calcineurin and calmodulin

et al. 2021

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Background Cystic echinococcosis (CE) is a disease caused by the larval stage of Echinococcus granulosus sensu lato (s.l.). The treatment of CE mainly relies on the use of benzimidazoles, which can commonly cause adverse side effects. Therefore, more efficient treatment options are needed. Drug repurposing is a useful approach for advancing drug development. We have evaluated the in vitro protoscolicidal effects of tropisetron and granisetron in E. granulosus sensu stricto (s.s.) and assessed the expression of the calcineurin (CaN) and calmodulin (CaM) genes, both of which have been linked to cellular signaling activities and thus are potentially promising targets for the development of drugs. Methods Protoscoleces (PSC) of E. granulosus (s.s.) (genotype G1) obtained from sheep hepatic hydatid cysts were exposed to tropisetron and granisetron at concentrations of 50, 150 and 250 µM for various periods of time up to 10 days. Cyclosporine A (CsA) and albendazole sulfoxide were used for comparison. Changes in the morphology of PSC were investigated by light microscopy and scanning electron microscopy. Gene expression was assessed using real-time PCR at the mRNA level for E. granulosus calcineurin subunit A (Eg-CaN-A), calcineurin subunit B (Eg-CaN-B) and calmodulin (Eg-CaM) after a 24-h exposure at 50 and 250 µM, respectively. Results At 150 and 250 µM, tropisetron had the highest protoscolicidal effect, whereas CsA was most effective at 50 µM. Granisetron, however, was less effective than tropisetron at all three concentrations. Examination of morphological alterations revealed that the rate at which PSC were killed increased with increasing rate of PSC evagination, as observed in PSC exposed to tropisetron. Gene expression analysis revealed that tropisetron at 50 μM significantly upregulated Eg-CaN-B and Eg-CaM expression while at 250 μM it significantly downregulated both Eg-CaN-B and Eg-CaM expressions; in comparison, granisetron decreased the expression of all three genes at both concentrations. Conclusions Tropisetron exhibited a higher efficacy than granisetron against E. granulosus (s.s.) PSC, which is probably due to the different mechanisms of action of the two drugs. The concentration-dependent effect of tropisetron on calcineurin gene expression might reflect its dual functions, which should stimulate future research into its mechanism of action and evaluation of its potential therapeutical effect in the treatment of CE. Graphic Abstract

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Molecular and biochemical characterization of calmodulin from Echinococcus granulosus

Cited by 16 publications

References 41 publications

Calmodulin-specific small interfering RNA induces consistent expression suppression and morphological changes in Echinococcus granulosus

Calmodulin-specific small interfering RNA induces consistent expression suppression and morphological changes in Echinococcus granulosus

Interactions between hydatid cyst and regulated cell death may provide new therapeutic opportunities

In vitro effects of tropisetron and granisetron against Echinococcus granulosus (s.s.) protoscoleces by involvement of calcineurin and calmodulin

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