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The alteration in signal transduction parameters induced by the excretory–secretory product from Giardia lamblia

Published online by Cambridge University Press:  14 September 2004

J. SHANT ,
S. GHOSH ,
S. BHATTACHARYYA ,
N. K. GANGULY  and
S. MAJUMDAR
J. SHANT
Affiliation:
Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh, India.
S. GHOSH
Affiliation:
Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh, India.
S. BHATTACHARYYA
Affiliation:
Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh, India.
N. K. GANGULY
Affiliation:
Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh, India.
S. MAJUMDAR
Affiliation:
Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh, India.
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Abstract

The mechanism by which Giardia lamblia exerts its pathogenicity is likely to be multifactorial. A 58 kDa enterotoxin was purified and characterized from the excretory–secretory product (ESP) of the parasite (Kaur et al. 2001). In the present study an attempt has been made to elucidate the mechanism of action of the ESP, a potentially important enterotoxin. A 41 kDa glycoprotein was identified in the mouse enterocyte membrane fraction with which the ESP interacted in a GM1-specific manner. The GTPase activity was reduced in enterocytes stimulated with the ESP, resulting in an increase in the level of adenylate cyclase-dependent cyclic adenosine monophosphate (cAMP). The activity of protein kinase A (PKA) in the enterocytes was also upregulated after ESP treatment. Ultimately, a significant increase in intracellular Ca2+ concentration and decrease in cytosolic Cl− level were noticed in ESP-stimulated mouse enterocytes. Thus it is possible that the enterotoxic ESP could bind to the 41 kDa glycoprotein (receptor?) on the enterocytes and activate the G-protein-mediated signal transduction pathway resulting in alteration of electrolyte transport.

Keywords

Giardia lambliaexcretory–secretory product (ESP)signal transductionG-proteinprotein kinase Aelectrolyte imbalance
Type
Research Article
Information
Parasitology , Volume 129 , Issue 4 , October 2004 , pp. 421 - 430
Copyright
2004 Cambridge University Press

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References

REFERENCES

ABEL, E. S., DAVIDS, B. J., ROBLES, L. D., LOFLIN, C. E., GILLIN, F. D. & CHAKRABARTI, R. (2001). Possible role of protein kinase A in cell motility and excystation of the early diverging eukaryote Giardia lamblia. Journal of Biological Chemistry 276, 10320–10329.CrossRefGoogle Scholar
ASAOKA, Y., OKA, M., YOSHIDA, K., SASAKI, Y. & NISHIZUKA, Y. (1992). Role of lysophosphatidylcholine in T-lymphocyte activation involvement of phospholipase A2 in signal transduction through protein kinase C. Proceedings of the National Academy of Sciences, USA 89, 6447–6451.CrossRefGoogle Scholar
BINDER, H. J. (1989). Absorption and secretion of water and electrolyte by small and large intestine. In Gastrointestinal Disease. Pathophysiology, Diagnosis and Management (ed. Steisenger, M. & Fordtran, J. S.), pp. 1022–1044. W.B. Saunders Company, Philadelphia.
BORIN, M. & SIFFERT, W. (1990). Stimulation by thrombin increases the cytosolic free Na+ concentration in human platelets. Journal of Biological Chemistry 265, 19543–19550.Google Scholar
BURET, A., HARDIN, J. A., OLSON, M. E. & GALL, D. G. (1992). Pathophysiology of small intestinal malabsorption in gerbils infected with Giardia lamblia. Gastroenterology 103, 503–513.CrossRefGoogle Scholar
BURET, A. G., MITCHELL, K., MUENCH, D. G. & SCOTT, K. G. E. (2002). Giardia lamblia disrupts tight junctional ZO-1 and increases permeability in non-transformed human small intestinal epithelial monolayers: effects of epidermal growth factor. Parasitology 125, 11–19.CrossRefGoogle Scholar
CHANG, E. B. & RAO, M. C. (1991). Intracellular mediators of intestinal electrolyte transport. In Diarrhoeal Diseases (ed. Field, M.), pp. 49–72. Elsevier, New York.
DAS, S., TRAYNOR-KAPLAN, A., KACHINTORN, U., ALEY, S. B. & GILLIN, F. D. (1994). GP49, an invariant GPI-anchored antigen of Giardia lamblia. Brazilian Journal of Medical and Biological Research 27, 463–469.Google Scholar
DEJONGE, H. R. (1983). Novel substrate proteins for cyclic nucleotide calcium and phospholipid – dependent protein kinases in the intestinal brush border. Gastroenterology Clinical Biology 7, 504.Google Scholar
DIAMOND, L. S., HARLOW, D. & CUNNICK, C. C. (1978). A new medium for the axenic cultivation of Entamoeba histolytica and other Entamoeba. Transactions of the Royal Society of Tropical Medicine and Hygiene 72, 431–432.CrossRefGoogle Scholar
DIXON, M. (1953). A nomogram for ammonium sulphate solutions. The Biochemical Journal 54, 457–458.CrossRefGoogle Scholar
DONOWITZ, M. & ASARKOF, N. (1982). Calcium dependence of basal electrolyte transport in rabbit ileum. American Journal of Physiology 243, G28–G35.CrossRefGoogle Scholar
DONOWITZ, M., WICKS, J., MADARA, J. L. & SHARP, G. W. G. (1985). Studies on the role of calmodulin in Ca2+ regulation of rabbit ileal Na+ and Cl− transport. American Journal of Physiology 248, G726–G740.CrossRefGoogle Scholar
DONOWTIZ, M., COHEN, M. E., GOULD, M. & SHARP, G. W. G. (1989). Elevated intracellular Ca2+ act through protein kinase C to regulate rabbit ileal NaCl absorption. Evidence for sequential control by Ca2+/Calmodulin and protein kinase C. Journal of Clinical Investigation 83, 1953–1962.Google Scholar
FANTINI, J., MARESCA, M., HAMMACHE, D., YAHI, N. & DELEZAY, O. (2000). Glycosphingolipid (GSL) microdomains as attachment platforms for host pathogens and their toxins on intestinal epithelial cells: activation of signal transduction pathways and perturbations of intestinal absorption and secretion. Glycoconjugate Journal 17, 173–179.CrossRefGoogle Scholar
FARTHING, M. J. G., PEREIRA, M. E. A. & KEUSCH, G. T. (1982). Giardia lamblia evaluation of roller bottle cultivation. Experimental Parasitology 54, 410–415.CrossRefGoogle Scholar
FAUBERT, G. (2000). Immune response to Giardia duodenalis. Clinical Microbiology Reviews 13, 35–54.CrossRefGoogle Scholar
FIELD, M., RAD, M. C. & CHANG, E. B. (1989). Intestinal electrolyte transport and diarrhoeal disease. Part 1, Part 2. The New England Journal of Medicine 321, 800–806, 879–883.Google Scholar
FROMM, D., GIANNELLA, R. A., FORMAL, S. B., QUIJANO, R. & COLLINS, H. (1974). Ion transport across isolated ileal mucosal invaded by Salmonella. Gastroenterology 66, 215–225.Google Scholar
GANGULY, N. K., GARG, S. K., VASUDEV, V., RADHAKRISHNAN, V., ANAND, B. C. & MAHAJAN, R. C. (1984). Prostaglandins E and F levels in mice infected with Giardia lamblia. Indian Journal of Medical Research 79, 755–759.Google Scholar
GANGULY, N. K., GARG, U. C., MAHAJAN, R. C., KANWAR, S. S., RAI, N. & WALIA, B. N. S. (1987). Intestine brush border calmodulin; key role in the regulation of NaCl transport of Giardia lamblia infected mice. Biochemical International 14, 249–256.Google Scholar
GEROK, W. (2000). Pathophysiology of chronic diarrhoea. Schweizerische Rundschreiben Medizinisch Praxis 12: 89, 1635–1641.Google Scholar
GOROWARA, S., GANGULY, N. K., MAHAJAN, R. C., GOYAL, J. & WALIA, B. N. S. (1991). Role of calcium and calmodulin in G. lamblia induced diarrhoea in mice. Journal of Diarrhoeal Disease Research 9, 111–117.Google Scholar
GOROWARA, S., GANGULY, N. K., MAHAJAN, R. C. & WALIA, B. N. S. (1992). Study on the mechanism of Giardia lamblia induced diarrhoea in mice. Biochimica et Biophysica Acta 1138, 122–127.CrossRefGoogle Scholar
GOROWARA, S., SAPRU, S., GANGULY, N. K. (1998). Role of intracellular second messenger and reactive oxygen species in the pathophysiology of V. cholerae 0139 treated rabbit ileum. Biochimica et Biophysica Acta 1407, 21–30.Google Scholar
HARDCASTLE, J., HARDCASTLE, P. T., NOBLE, J. M. (1984). The involvement of calcium in the intestinal response to secretagogues in rat. The Journal of Physiology 355, 465–478.CrossRefGoogle Scholar
HOQUE, K. M., PAL, A., NAIR, G. B., CHATTOPADHYAY, S. & CHAKRABORTI, M. K. (2001). Evidence of calcium influx across the plasma membrane depends upon the initial rise of cytosolic calcium with activation of IP3 in rat enterocytes by heat-stable enterotoxin of Vibrio cholerae non-01. FEMS Microbiology Letters 196, 45–50.CrossRefGoogle Scholar
JIMENEZ, J. C., FONTAINE, J., GRZYCH, J. M., DEI-CAS, E. & CAPRON, M. (2004). Systemic and mucosal responses to oral administration of excretory and secretory antigens from Giardia intestinalis. Clinical and Diagnostic Laboratory Immunology 11, 152–160.CrossRefGoogle Scholar
KANWAR, R. K., GANGULY, N. K., KANWAR, J. R., KUMAR, L. & WALIA, B. N. S. (1994). Impairment of Na+, K+-ATPase activity following enterotoxigenic Campylobacter jejuni infection: changes in Na, Cl and 3-0-methyl-D-glucose transport in vitro in rat ileum. FEMS Microbiology Letters 124, 381–386.CrossRefGoogle Scholar
KAPER, K. B., FASANO, A. & TRUCKSIS, M. (1994). Toxins of Vibrio cholerae. In Vibrio cholerae and Cholera (ed. Wachsmuth, I. K., Blake, P. A. & Olsvik, O.), pp. 145–176. American Society for Microbiology, Washington, DC.CrossRef
KAUR, H., SAMRA, H., GHOSH, S., VINAYAK, V. K. & GANGULY, N. K. (1999). Immune effector responses to an excretory-secretory product of Giardia lamblia. FEMS Immunology and Medical Microbiology 23, 93–105.CrossRefGoogle Scholar
KAUR, H., GHOSH, S., SAMRA, H., VINAYAK, V. K. & GANGULY, N. K. (2001). Identification and characterization of an excretory-secretory product from Giardia lamblia. Parasitology 123, 347–356.CrossRefGoogle Scholar
KHURANA, S., GANGULY, N. K., KHULLAR, M., PANIGRAHI, D. & WALIA, B. N. S. (1991). Studies on the mechanism of Salmonella typhimurium enterotoxin induced diarrhoea. Biochimica et Biophysica Acta 1097, 171–176.CrossRefGoogle Scholar
LAEMMLI, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, London 227, 680–685.CrossRefGoogle Scholar
LLOYD, D., RALPHS, J. R. & HARRIS, J. C. (2002). Hydrogen production in Giardia intestinalis, a eukaryote with no hydrogenosomes. Trends in Parasitology 18, 155–156.CrossRefGoogle Scholar
MINKE, W. E., ROACH, C., HOL, W. G. J. & VERLINDE, L. M. J. (1999). Structure based exploration of the ganglioside GM1 binding sites of E. coli heat labile enterotoxin and cholera toxin for the discovery of receptor antagonists. Biochemistry 38, 5684–5692.Google Scholar
PACE, J. L. & GALAN, J. E. (1994). Measurement of free intracellular calcium levels in epithelial cells as a consequence of bacterial invasion. Methods in Enzymology 236, 482–485.CrossRefGoogle Scholar
PETERSON, J. W., MOLINA, N. C., HOUSTON, C. W., FADER, R. C. (1983). Elevated cAMP in intestinal epithelial cells during experimental cholera and salmonellosis. Toxicon 21, 761–775.CrossRefGoogle Scholar
PINKUS, L. H. (1981). Separation and use of enterocytes. Methods in Enzymology 77, 154–162.CrossRefGoogle Scholar
SAMRA, H. K., GANGULY, N. K., GARG, U. C., GOYAL, J. & MAHAJAN, T. (1988). Effect of excretory-secretory products of Giardia lamblia in glucose and plenylamine transport in the small intestine of Swiss albino mice. Biochemistry International 17, 801–812.Google Scholar
SEARS, C. L. & KAPER, J. B. (1996). Enteric bacterial toxins: mechanisms of action and linkage to intestinal secretion. Microbiological Reviews 60, 167–215.Google Scholar
SHANT, J., BHATTACHARYYA, S., GHOSH, S., GANGULY, N. K. & MAJUMDAR, S. (2003). A potentially important excretory-secretory product of Giardia lamblia. Experimental Parasitololy 102, 178–186.Google Scholar
SVOBODA, P. & NOVOTNY, J. (2002). Hormone-induced subcellular redistribution of trimeric G proteins. Cellular and Molecular Life Science 59, 501.CrossRefGoogle Scholar
SWEENEY, M. (1995). Measurement of the GTPase activity of signal-transduction G-proteins in neuronal membranes. In Methods of Molecular Biology, Vol. 41: Signal Transduction Protocols (ed. Kendall, D. A. & Hill, S. J.), pp. 51–61. Humana Press Inc., Potowa NT.
TOWBIN, H., STAEHELIN, T. & GORDON, J. (1979). Electrophoretic transfer of protein from polyacrylamide gels to nitrocellulose sheets. Procedure and some applications. Proceedings of the National Academy of Sciences, USA 76, 4350–4354.CrossRefGoogle Scholar
TOYODA, S., LEE, P. C. & LABENTHAL, E. (1985). Physiological factors controlling release of enterokinase from rat enterocytes. Digestive Disease Science 30, 1174–1180.CrossRefGoogle Scholar
VERKMAN, A. S., SELLERS, M. C., CHAO, A. C., LEUNG, T. & KETCHAM, K. (1989). Synthesis and characterization of improved chloride-sensitive fluorescent indicators for biological applications. Analytical Biochemistry 178, 355–361.CrossRefGoogle Scholar
ZIMMERMAN, T. W., DOBBINS, J. W. & BINDER, H. J. (1983). Role of calcium in the regulation of colonic secretion in rat. American Journal of Physiology 244, G552–G560.CrossRefGoogle Scholar