Skip to main content Accessibility help
×
×
Home

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

  • A.G. Fuchs (a1), C.I. Echeverría (a1), F.G. Pérez Rojo (a1), E.A. Prieto González (a1) and E.J.A. Roldán (a1)...
Abstract

Bisphosphonates have been proposed as pharmacological agents against parasite and cancer cell growth. The effect of these compounds on helminthic cell viability and acellular compartment morphology, however, has not yet been studied. The effects of different types of bisphosphonates, namely etidronate (EHDP), pamidronate (APD), alendronate (ABP), ibandronate (IB) and olpadronate (OPD), and their interaction with amiloride, 1,25-dihydroxycholecalciferol (D3) and proline were evaluated on a cell line derived from bovine Echinococcus granulousus protoscoleces (EGPE) that forms cystic colonies in agarose. The EGPE cell line allowed testing the effect of bisphosphonates alone and in association with other compounds that could modulate calcium apposition/deposition, and were useful in measuring the impact of these compounds on cell growth, cystic colony formation and calcium storage. Decreased cell growth and cystic colony formation were found with EHDP, IB and OPD, and increased calcium storage with EHDP only. Calcium storage in EGPE cells appeared to be sensitive to the effect of amiloride, D3 and proline. Proline decreased calcium storage and increased colony formation. Changes in calcium storage may be associated with degenerative changes of the cysts, as shown in the in vitro colony model and linked to an adenosine triphosphate (ATP) decrease. In conclusion, bisphosphonates could be suitable tempering drugs to treat cestode infections.

Copyright
Corresponding author
*Fax: (54) 11 4301 5240 extension 2 E-mail: Alicia.Fuchs@uai.edu.ar
References
Hide All
Cabezón, C., Cabrera, G., Paredes, R., Ferreira, A. & Galanti, N. (2008) Echinococcus granulosus calreticulin: molecular characterization and hydatid cyst localization. Molecular Immunology 45, 14311438.
Casaravilla, C., Brearley, C., Soulé, S., Fontana, C., Veiga, N., Bessio, M.I., Ferreira, F., Kremer, C. & Díaz, A. (2006) Characterization of myo-inositol hexakisphosphate deposits from larval Echinococcus granulosus. The FEBS Journal 273, 31923203.
Chowdhury, N. & Singh, R. (1993) Distribution of some elements in hydatid cysts of Echinococcus granulosus from buffalo (Bubalus bubalis). Journal of Helminthology 67, 112114.
Cukrowski, I., Popović, L., Barnard, W., Paul, S.O., van Rooyen, P.H. & Liles, D.C. (2007) Modeling and spectroscopic studies of bisphosphonate–bone interactions. The Raman, NMR and crystallographic investigations of Ca-HEDP complexes. Bone 41, 668678.
Cumino, A.C., Elisondo, M.C. & Denegri, G.M. (2009) Flubendazole interferes with a wide spectrum of cell homeostatic mechanisms in Echinococcus granulosus protoscoleces. Parasitology International 58, 270277.
Cumino, A.C., Lamenza, P. & Denegri, G.M. (2010) Identification of functional FKB protein in Echinococcus granulosus: its involvement in the protoscolicidal action of rapamycin derivates and in calcium homeostasis. International Journal for Parasitology 40, 651661.
Daryani, A., Sharif, M., Amouei, A. & Nasrolahei, M. (2009) Fertility and viability rates of hydatid cysts in slaughtered animals in the Mazandaran Province, Northern Iran. Tropical Animal Health and Production 41, 17011705.
Drake, M.T., Clarke, B.L. & Khosla, S. (2008) Bisphosphonates: mechanism of action and role in clinical practice. Mayo Clinic Proceedings 83, 10321045.
Echeverría, C.I., Isolabella, D.M., Prieto, E.A.G., Leonardelli, A., Prada, L., Perrone, A. & Fuchs, A.G. (2010) Morphological and biological characterization of cell line developed from bovine Echinococcus granulosus. In Vitro Cellular and Development Biology—Animal 46, 781792.
Epping, K. & Brehm, K. (2011) Echinococcus multilocularis: molecular characterization of EmSmadE, a novel BR-Smad involved in TGF-β and BMP signaling. Experimental Parasitology 129, 8594.
Farach-Carson, M.C. & Ridall, A.L. (1998) Dual 1,25-dihydroxyvitamin D3 signal response pathways in osteoblasts: cross-talk between genomic and membrane-initiated pathways. American Journal of Kidney Diseases 31, 729742.
Frayha, G.J. & Haddad, R. (1980) Comparative chemical composition of protoscoleces and hydatid cyst fluid of Echinococcus granulosus (Cestoda). International Journal for Parasitology 10, 359364.
Giorgio, A., Tarantino, L., Francica, G., Mariniello, N., Aloisio, T., Soscia, E. & Pierri, G. (1992) Unilocular hydatid liver cysts: treatment with US-guided, double percutaneous aspiration and alcohol injection. Radiology 184, 705710.
Grosman, C. & Reisin, I.L. (1995) Echinococcus granulosus: partial characterization of the conductive properties of two cation channels from protoscoleces of the ovine strain, reconstituted on planar lipid bilayers. Experimental Parasitology 81, 546555.
Grosman, C. & Reisin, I.L. (1997) Interconverting gating modes of a nonselective cation channel from the tapeworm Echinococcus granulosus reconstituted on planar lipid bilayers. Journal of Membrane Biology 158, 8794.
Guenther, H.L., Guenther, H.E. & Fleisch, H. (1981) The effects of 1-hydroxyethane-1,1-diphosphonate and dichloromethanediphosphonate on collagen synthesis by rabbit articular chondrocytes and rat bone cells. Biochemical Journal 196, 293301.
Guerret, S., Vuitton, D.A., Liance, M., Pater, C. & Carbillet, J.P. (1998) Echinococcus multilocularis: relationship between susceptibility/resistance and liver fibrogenesis in experimental mice. Parasitology Research 84, 657667.
Halder, S.K., Goodwin, J.S. & Al-Hendy, A. (2011) 1,25-Dihydroxyvitamin D3 reduces TGF-beta3-induced fibrosis-related gene expression in human uterine leiomyoma cells. Journal of Clinical Endocrinology and Metabolism 96, E754E762.
Heath, D.D., Jensen, O. & Lightowlers, M.W. (2003) Progress in control of hydatidosis using vaccination – a review of formulation and delivery of the vaccine and recommendation for practical use in control programmes. Acta Tropica 85, 133143.
Hemphill, A., Spicher, M., Stadelmann, B., Mueller, J., Naguleswaran, A., Gottstein, B. & Walker, M. (2007) Innovative chemotherapeutical treatment options for alveolar and cystic echinococcosis. Parasitology 134, 16571670.
Ibarra, C. & Reisin, I.L. (1994) Echinococcus granulosus: characterization of the electrical potential of the syncytial tegument of protoscoleces incubated in vitro – effect of inhibitors. Experimental Parasitology 78, 400409.
Irigoin, F., Casaravilla, C., Iborra, F., Sim, R.B., Ferreira, F. & Díaz, A. (2004) Unique precipitation and exocytosis of a calcium salt of myo-inositol hexakisphosphate in larval Echinococcus granulosus. Journal of Cellular Biochemistry 93, 12721281.
Kavanagh, K.L., Guo, K., Dunford, J.E., Wu, X., Knapp, S., Ebetino, F.H., Rogers, M.J., Russell, R.G.G. & Oppermann, U. (2006) The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proceedings of the National Academy of Science of the United States of America 103, 78297834.
Kusters, J.M.A.M., Dernison, M.M., van Meerwijk, W.P.M., Ypey, D.L., Theuvenet, A.P.R. & Gielen, C.C.A.M. (2005) Stabilizing role of calcium store-dependent plasma membrane calcium channels in action-potential firing and intracellular calcium oscillations. Biophysical Journal 89, 37413756.
Lidor, C., Meyer, M.S., Wasserman, R.H. & Edelstein, S. (1987) The effect of disodium ethane-1-hydroxy-1,1-diphosphonate on the metabolism of calcitriol in chicks. Biochemical Journal 243, 7578.
Mahmoud, L.H. & el-Garhy, M.F. (2002) A histochemical study on the hydatid cyst and electron microscopy of the hydatid sand of Echinococcus granulosus. Journal of the Egyptian Society of Parasitology 32, 647656(Abstract).
Masud, T., Mulcahy, B., Thompson, A.V., Donnelly, S., Keen, R.W., Doyle, D.V. & Spector, T.D. (1998) Effects of cyclical etidronate combined with calcitriol versus cyclical etidronate alone on spine and femoral neck bone mineral density in postmenopausal osteoporotic women. Annals of the Rheumatic Diseases 57, 346349.
Moro, P. & Schantz, P.M. (2006) Cystic echinococcosis in the Americas. Parasitology International 55, s181s186.
Ortiz-Gómez, A., Jiménez, C., Estévez, A.M., Carrero-Lérida, J., Ruiz-Pérez, L.M. & González-Pacanowska, D. (2006) Farnesyl diphosphate synthase is a cytosolic enzyme in Leishmania major promastigotes and its overexpression confers resistance to risedronate. Eukaryotic Cell 5, 10571064.
Panda, D.K., Miao, D., Bolivar, I., Li, J., Huo, R., Hendy, G.N. & Goltzman, D. (2004) Inactivation of the 25-hydroxyvitamin D 1α-hydroxylase and vitamin D receptor demonstrates independent and interdependent effects of calcium and vitamin D on skeletal and mineral homeostasis. Journal of Biological Chemistry 279, 1675416766.
Phang, J.M., Liu, W., Hancock, C. & Christian, K.J. (2012) The proline regulatory axis and cancer. Frontiers in Oncology 2, 60.
Sanz-Rodriguez, C.E., Concepción, J.L., Pekerar, S., Oldfield, E. & Urbina, J.A. (2007) Bisphosphonates as inhibitors of Trypanosoma cruzi kexokinase: kinetic and metabolic studies. Journal of Biological Chemistry 282, 1237712387.
Sato, M., Grasser, W., Endo, N., Akins, R., Simmons, H., Thompson, D.D., Golub, E. & Rodan, G.A. (1991) Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. Journal of Clinical Investigation 88, 20952105.
Shao, W., Orlando, R.C. & Awayda, M.S. (2005) Bisphosphonates stimulate an endogenous nonselective cation channel in Xenopus oocytes: potential mechanism of action. American Journal of Physiology – Cell Physiology 289, C248C256.
Smith, S.A. & Richards, K.S. (1993) Ultrastructure and microanalyses of the calcareous corpuscles of the protoscoleces of Echinococcus granulosus. Parasitology Research 79, 245250.
Spillotis, M. & Brehm, K. (2004) Echinocuccus multilocularis: identification and molecular characterization of a Ral-like small GTP-binding protein. Experimental Parasitology 107, 163172.
Vazquez, G., Santillan, G., Boland, R., Roldán, E. & Pérez-Lloret, A. (2003) Modulation of cytosolic calcium levels in osteoblast-like osteosarcoma cells by olpadronate and its amino-derivative IG-9402. Calcified Tissue International 72, 215221.
Vidor, E., Piens, M.A., Abbas, M. & Petavy, A.F. (1986) Hydatid cyst fluid (Echinococcus granulosus) biochemistry. Influence of site on cyst permeability. Annales de Parasitologie Humaine et Comparee 61, 333340(Abstract).
Zurabian, R., Carrero, J.C., Rodríguez-Contreras, D., Willms, K. & Laclette, J.P. (2005) Antigenic proteins associated with calcareous corpuscules of Taenia solium; partial characterization of a calcium-binding protein. Archives of Medical Research 36, 49.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Journal of Helminthology
  • ISSN: 0022-149X
  • EISSN: 1475-2697
  • URL: /core/journals/journal-of-helminthology
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed