Proline modulates the effect of bisphosphonate on calcium levels and adenosine triphosphate production in cell lines derived from bovine <i>Echinococcus granulosus</i> protoscoleces

Fuchs, Alicia Graciela; Echeverría, Claudia; Rojo, Fernando G. Pérez; González, Elio Antonio Prieto; Roldán, Ernesto

doi:10.1017/s0022149x13000436

Cited by 4 publications

(3 citation statements)

References 38 publications

(43 reference statements)

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“…Amino-bisphosphonates caused an ATP decrease in a tapeworm model (53), but the molecular mechanism has not been described. In T. brucei, ATP generation is probably not affected directly by the decrease of TbSPPS.…”

Section: Discussionmentioning

confidence: 99%

Solanesyl Diphosphate Synthase, an Enzyme of the Ubiquinone Synthetic Pathway, Is Required throughout the Life Cycle of Trypanosoma brucei

et al. 2014

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h Ubiquinone 9 (UQ9), the expected product of the long-chain solanesyl diphosphate synthase of Trypanosoma brucei (TbSPPS), has a central role in reoxidation of reducing equivalents in the mitochondrion of T. brucei. The ablation of TbSPPS gene expression by RNA interference increased the generation of reactive oxygen species and reduced cell growth and oxygen consumption. The addition of glycerol to the culture medium exacerbated the phenotype by blocking its endogenous generation and excretion. The participation of TbSPPS in UQ synthesis was further confirmed by growth rescue using UQ with 10 isoprenyl subunits (UQ10). Furthermore, the survival of infected mice was prolonged upon the downregulation of TbSPPS and/or the addition of glycerol to drinking water. TbSPPS is inhibited by 1-[(n-oct-1-ylamino)ethyl] 1,1-bisphosphonic acid, and treatment with this compound was lethal for the cells. The findings that both UQ9 and ATP pools were severely depleted by the drug and that exogenous UQ10 was able to fully rescue growth of the inhibited parasites strongly suggest that TbSPPS and UQ synthesis are the main targets of the drug. These two strategies highlight the importance of TbSPPS for T. brucei, justifying further efforts to validate it as a new drug target.

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Section: Discussionmentioning

confidence: 99%

Solanesyl Diphosphate Synthase, an Enzyme of the Ubiquinone Synthetic Pathway, Is Required throughout the Life Cycle of Trypanosoma brucei

et al. 2014

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“…Consistent with the need to improve the serological diagnosis of CE, in our laboratory, we have previously developed a cell line from bovine E granulosus G1 protoscoleces, genotyped from its mitochondrial DCO1 sequence, which we called EGPE . This cell line grows in axenic liquid medium, developing two defined morphological stages (Figure ): up to 7 days of growth, cells are organized in clusters of small cells in suspension, a stage referred to as “short,” whereas, after 20 days, cells aggregate and attach to the released floating membranes, a stage referred to as “long”.…”

Section: Introductionmentioning

confidence: 97%

Detection of Echinococcus granulosus sensu lato infection by using extracts derived from a protoscoleces G1 cell line

Maglioco

Gentile²,

Venturi

et al. 2019

Parasite Immunology

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Cystic echinococcosis (CE), also called hydatidosis, is a zoonotic parasitosis worldwide distributed 1 caused by the larval stage (metacestode) of Echinococcus granulosus sensu lato. This hermaphrodite worm develops in the intestine of domestic and wild canids, and then its gravid proglottid releases the eggs to the faeces, contaminating the environment. The eggs ingested by the intermediate host hatch in the duodenum, and the oncosphere then penetrates the intestinal wall, migrates, and becomes trapped in the host's organs, where it becomes metacestode. The parasite's cycle is accomplished when the infected organ from the intermediate host is ingested by the definitive host (canids). 2 Humans, as intermediate accidental hosts, who are more exposed to the infection in unsanitary conditions, develop a parasitic disease involving the encystment of the larvae in different organs (the liver in 70%-80% of the cases, the lungs in 20%-30% of the cases and other organs with lower frequency), 3 resulting in a wide spectrum of clinical manifestations. Mitochondrial DNA has so far allowed identifying eight Echinococcus granulosus sensu lato genotypes (G1, G3-G8, and G10). 4,5 Four of these genotypes, G1 in sheep, G5 in cattle, G6 in camelids and G7 in swine, have been detected in Argentina. 4 Abstract Cystic echinococcosis (CE) can be diagnosed by means of several serological approaches, but their results vary among laboratories due to the molecular characteristics of the reference antigens used. Thus, this study aimed to address both the relevance of an EGPE cell line previously obtained from Echinococcus granulosus protoscoleces G1 and the complexity of the immune response by using two different in vitro growth stages as separate sources of parasite antigens. The serum reactivity was investigated by western blotting (WB) in 21 CE patients from an endemic area in a matched case-control design and also in seven experimentally infected sheep and five healthy control sheep. EGPE-antigen-human serum sensitivity by WB was higher than that of hydatid fluid (HF) WB, ELISA and DD5 (P < .05, Chi-square test). EGPE protein extract was immunogenic in mice and hyperimmune plasma reacted with HF proteins, and AgB2 expression was detected by molecular analysis. Proteins of 37 to 60 kDa were recognized by 95.24% of the CE patients' sera but, with poor specificity. Statistically significant differences were found between serum protein extract recognition at 7 and 20 days of cell growth. The EGPE cell line is a laboratory source of antigens for improvement of CE serological diagnosis. K E Y W O R D S cell line extract, Cystic echinococcosis, human, immunoblot, parasite, sera, sheep

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“…As one of the antigenic components in echinococcus cyst fluid, protein plays an important role in the course of the disease and is an important index to reflect the biological activity of echinococcus, and the change of its content can reflect the physiological state of echinococcus [ 9 ]. The normal echinococcosis cyst fluid contains a certain amount of Ca2+, and in echinococcosis degeneration, elevated Ca2+ content is one of the signs of improvement of CE [ 10 ]. In addition to protein content and Ca2+ concentration, changes in the wet weight and inhibition rate of cysts and some other parameters were observed in this experiment.…”

Section: Introductionmentioning

confidence: 99%

Outcomes of Radiotherapy for Osseous Echinococcosis of Meriones meridianus

Luo

Mahan

et al. 2020

BioMed Research International

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Background. Osseous cyst echinococcosis (CE) is an infectious disease that causes disability and deformity in patients, yet there is still no satisfactory treatment. Focusing on the feasibility and prognosis of radiotherapy as an adjuvant or palliative treatment for osseous CE, this study investigated the outcome of Meriones meridianus with osseous CE after radiotherapy. Methods. The study utilized a comparison control group design with three groups of gerbils, and 240 osseous CE gerbils were randomly divided into control, 40Gy/5times, and 50Gy/5times groups. Different doses of radiotherapy were given to the gerbils, and then, the effects of radiotherapy on gerbils and lesions were observed at 3 and 6 months after radiotherapy. Statistical analysis was done using χ2 test, unpaired t-test, and one-way ANOVA. Results. Significant changes (P<0.05) were achieved between the three groups in terms of seven parameters at 3 and 6 months, including the number of dead gerbils and lesion sites with ulceration and infection, number of dead scolices, protein content, Ca2+ concentration, the maximum diameter of lesion site, and wet weight of cysts. Except for the number of dead gerbils and lesion sites with ulceration and infection, all other parameters were observed a big difference between 3 months and 6 months in the 50Gy/5times group. Conclusion. Radiotherapy at a dose of 50 Gy has inhibitory and therapeutic effects on osseous CE in gerbils, and radiotherapy could probably be a treatment option for persistent or recurrent osseous CE.

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Proline modulates the effect of bisphosphonate on calcium levels and adenosine triphosphate production in cell lines derived from bovine Echinococcus granulosus protoscoleces

Cited by 4 publications

References 38 publications

Solanesyl Diphosphate Synthase, an Enzyme of the Ubiquinone Synthetic Pathway, Is Required throughout the Life Cycle of Trypanosoma brucei

Solanesyl Diphosphate Synthase, an Enzyme of the Ubiquinone Synthetic Pathway, Is Required throughout the Life Cycle of Trypanosoma brucei

Detection of Echinococcus granulosus sensu lato infection by using extracts derived from a protoscoleces G1 cell line

Outcomes of Radiotherapy for Osseous Echinococcosis of Meriones meridianus

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