The alteration in signal transduction parameters induced by the excretory-secretory product from Giardia lamblia.
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.
Shant
J
J
Department of Experimental Medicine and Biotechnology, Post-Graduate Institute of Medical Education and Research, Chandigarh, India. jas_shant@rediffmail.com
Ghosh
S
S
Bhattacharyya
S
S
Ganguly
N K
NK
Majumdar
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003967:Diarrhea / Q000378:metabolism / Q000469:parasitology; D020895:Enterocytes / Q000187:drug effects / Q000201:enzymology / Q000469:parasitology; D004768:Enterotoxins / Q000302:isolation & purification / Q000494:pharmacology*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology; D016829:Giardia lamblia / Q000737:chemistry* / Q000378:metabolism / Q000472:pathogenicity; D005873:Giardiasis / Q000469:parasitology; D007411:Intestinal Diseases, Parasitic / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D004768:Enterotoxins; D015800:Protozoan Proteins; D012964:Sodium; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D002118:Calcium