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Activation of protein kinase C by phorbol esters disrupts the tegument of Schistosoma mansoni

Published online by Cambridge University Press:  06 April 2009

P. M. Wiest
Affiliation:
Division of Geographic Medicine, The Department of Medicine, The Miriam Hospital and The International Health Institute, Brown University and Division of Biology and Medicine, Brown University, Providence, RI 02906, USA
S. S. Kunz
Affiliation:
Division of Geographic Medicine, The Department of Medicine, The Miriam Hospital and The International Health Institute, Brown University and Division of Biology and Medicine, Brown University, Providence, RI 02906, USA
K. R. Miller
Affiliation:
Division of Geographic Medicine, The Department of Medicine, The Miriam Hospital and The International Health Institute, Brown University and Division of Biology and Medicine, Brown University, Providence, RI 02906, USA

Summary

The tegument of the human parasite Schistosoma mansoni is critical for parasite survival within the mammalian host. The role of protein kinase C (PKC), a major effector molecule in the phosphoinositide pathway, in maintaining the structural organization of this syncytial layer was examined in adult worms. Phorbol 12-myristate, 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB), phorbol esters that activate PKC, induced formation of surface vesicles as determined by light and scanning electron microscopy. Similar results were seen with sn-2-dioctanoyl-glycerol, a synthetic analogue of diacylglycerol. No effect was seen in parasites incubated with 4-a-phorbol ester or a isomers of PMA or PDB, compounds that do not activate PKC. Vesicle formation was reversible in parasites treated with sn-2-dioctanoyl-glycerol but not with phorbol esters. The tegument of male worms was more sensitive to the effect of phorbol esters than females. Transmission electron microscopy revealed vacuolization of the tegument. These data suggest that signal transduction pathways may have a critical role in the maintenance of the structural integrity of the tegument of parasitic helminths.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1994

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References

REFERENCES

Andrews, P. (1985). Praziquantel: mechanism of antischistosomal activity. Journal of Pharmacology and Experimental Therapeutics 29, 129–56.Google Scholar
Berra, E., Diaz-Meco, M. T., Dominiques, I., Municio, M. M., Sanz, L., Lozano, J., Chaphin, R. S. & Moscat, J. (1993). Protein kinase C G isoform is critical for mitogenic signal transduction. Cell 74, 555–63.CrossRefGoogle Scholar
Berridge, M. J. (1993). Inositol triphosphate and calcium signaling. Nature, London 361, 315–25.CrossRefGoogle Scholar
Bershadsky, A. D., Ivanova, O. Y., Lyass, L. A., Pletyushkina, O. Y., Vasileiu, J. M. & Gifand, I. M. (1990). Cytoskeletal reoganizations responsible for the phorbol ester-induced formation of cytoplasmic processes: possible involvement of intermediate filaments. Proceedings of the National Academy of Sciences, USA 87, 1884–8.CrossRefGoogle ScholarPubMed
Blair, K. L., Bennett, J. L. & Pax, R. A. (1988). Schistosoma mansoni: evidence for protein kinase C-like modulation of muscle activity. Experimental Parasitology 66, 243–52.Google Scholar
Busch, A. E., Varnum, M. D., North, R. A. & Adelman, J. P. (1992). An amino acid mutation in a potassium channel that prevents inhibition by protein kinase C. Science 255, 1705–7.CrossRefGoogle Scholar
Capron, A., Dessaint, J. P., Capron, M., Ouma, J. H. & Butterworth, A. E. (1987). Immunity to schistosomes: progress toward vaccine. Science 238, 1065–72.CrossRefGoogle ScholarPubMed
Chappell, L. H. (1987). The interaction between drugs and parasites. Parasitology 96, S167S193.CrossRefGoogle Scholar
Ebeling, J. G. G., Vandenbark, G. R., Kuhn, L. J., Ganong, B. R., Bell, R. M. & Niedel, J. E. (1985). Diacylglycerol mimics phorbol diester induction of leukemic cell differentiation. Proceedings of the National Academy of Sciences, USA 82, 815–19.CrossRefGoogle ScholarPubMed
Exton, J. H. (1990). Signaling through phosphatidylcholine breakdown. Journal of Biological Chemistry 265, 14.CrossRefGoogle ScholarPubMed
Hockley, D. J. & McLaren, D. J. (1973). Schistosoma mansoni changes in the outer membrane of the tegument during development from cercaria to adult worms. International Journal for Parasitology 3, 1325.Google Scholar
Kikkawa, U. & Nishizuka, Y. (1986). The role of protein kinase C in transmembrane signaling. Annual Reviews of Cell Biology 2, 149–78.Google Scholar
Matsumoto, Y., Perry, G., Levine, R. J. C., Blanton, R., Mahmoud, A. A. F. & Aikawa, M. (1988). Paramyosin and actin in schistosomal teguments. Nature, London 333, 76–8.CrossRefGoogle ScholarPubMed
MacGregor, A. N. & Shaw, S. J. (1990). Immunocyto-chemistry of cytoskeletal proteins in adult Schistosoma mansoni. International Journal for Parasitology 20, 279–84.CrossRefGoogle Scholar
Majerus, P. W., Connally, T. M., Bansal, V. S., Inhorn, R. C., Ross, T. S. & Lips, D. L. (1988). Inositol phosphates: synthesis and degradation. Journal of Biological Chemistry 263, 3051–4.Google Scholar
Niedel, J. E., Kuhn, L. J. & Vandenbark, G. R. (1983). Phorbol diester receptor copurifies with protein kinase C. Proceedings of the National Academy of Sciences, USA 80, 3640.CrossRefGoogle ScholarPubMed
Nishizuka, Y. (1984). The role of protein kinase C in cell surface signal transduction and tumour production. Nature, London 308, 693–8.CrossRefGoogle Scholar
Oaks, J. A., Cain, G. D., Mower, D. A. & Raj, R. K. (1981). Disruption and removal of the tegument from Schistosoma mansoni. Journal of Parasitology 67, 761–75.CrossRefGoogle ScholarPubMed
Papadopoulos, V. & Hall, P. F. (1989). Isolation and characterization of protein kinase C from Y-1 adrenal cell cytoskeleton. Journal of Cell Biology 108, 553–9.CrossRefGoogle ScholarPubMed
Pearce, E. J. & Sher, A. (1987). Mechanisms of immune evasion in schistosomiasis. In Contributions to Microbiology and Immunology, vol 8, (ed. Cruse, J. M. & Lewis, R. E.) Basel: Karger.Google Scholar
Shearman, M. S., Sekigushi, K. & Nishizuka, Y. (1989). Modulation of ion channel activity: a key function of the protein kinase C enzyme family. Pharmacological Reviews 41, 211–37.Google Scholar
Smithers, S. R. & Terry, R. J. (1965). The infection of laboratory hosts with cercariae of Schistosoma mansoni and recovery of adult worms. Parasitology 55, 695704.CrossRefGoogle ScholarPubMed
Wiest, P. M., Tartakoff, A. M., Aikawa, M. & Mahmoud, A. A. F. (1988). Inhibition of heptalaminate surface membrane maturation in schistosomula of Schistosoma mansoni. Proceedings of the National Academy of Sciences, USA 85, 3825–9.CrossRefGoogle Scholar
Wiest, P. M., Burnham, D., Olds, G. R. & Bowen, W. D. (1992 a). Developmental regulation of protein kinase C activity in Schistosoma mansoni. American Journal of Tropical Medicine and Hygiene 46, 358–65.CrossRefGoogle ScholarPubMed
Wiest, P. M., Burnham, D., Olds, G. R. & Bowen, W. D. (1992 b). Schistosoma mansoni: characterization of the phosphoinositide response. Experimental Parasitology 74, 3845.CrossRefGoogle ScholarPubMed
Wilson, S. P. (1990). Regulation of chromaffin cell secretion and protein kinase C activity by chronic phorbol ester treatment. Journal of Biological Chemistry 265, 648–51.Google Scholar
Witters, L. A. & Blackshear, P. J. (1987). Protein kinase C-mediated phosphorylation in intact cells. Methods in Enzymology 141, 412–24.CrossRefGoogle ScholarPubMed
Xiao, S., Friedman, P. A., Catto, B. A. & Webster, L. T. (1984). Praziquantel-induced vesicle formation in the tegument of male Schistosoma mansoni is calcium dependent. Journal of Parasitology 70, 177–9.Google Scholar
Xu, H., Miller, S., Van Keulin, H., Wawrzynsli, M. R., Rebosh, D. M. & Loverde, P. T. (1989). Schistosoma mansoni tropomyosin: cDNA characterization, sequence, expression and gene product localization. Experimental Parasitology 69, 373–92.Google Scholar
Zhou, Y. & Podesta, R. B. (1989). Effects of serotonin (5HT) and complement C3 on the synthesis of the surface membrane precursors of adult Schistosoma mansoni. Journal of Parasitology 75, 333–43.Google Scholar