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Am J Physiol Gastrointest Liver Physiol 297: G52-G59, 2009. First published May 7, 2009; doi:10.1152/ajpgi.90599.2008
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MUCOSAL BIOLOGY

Uptake and fate of ganglioside GD3 in human intestinal Caco-2 cells

Kareena L. Schnabl,1,3 Marjorie Larcelet,2 Alan B. R. Thomson,1,3 and Michael T. Clandinin1,3

1Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada; 2École nationale supérieure de biologie appliquée à la nutrition et à l'alimentation (ENSBANA), Dijon, France; and 3Alberta Institute for Human Nutrition, University of Alberta, Edmonton, Alberta, Canada

Submitted 16 October 2008 ; accepted in final form 4 May 2009

Ganglioside GD3 is a glycosphingolipid found in colostrum, developing tissues, and tumors and is known to regulate cell growth, differentiation, apoptosis, and inflammation. Feeding a GD3-enriched diet to rats increases GD3 in intestinal lipid rafts and blood. The mechanism, efficiency, and fate of ganglioside absorption by human enterocytes have not been investigated. A model to study GD3 uptake by human intestinal cells was developed to test the hypothesis that enterocyte GD3 uptake is time and concentration dependent, with uptake efficiency and fate influenced by route of delivery. Caco-2 cells were exposed to GD3 on the apical or basolateral membrane (BLM) side for 6, 24, and 48 h. GD3 uptake, retention, transfer, and metabolism was determined. GD3 uptake across the apical and BLM was time and concentration dependent and reached a plateau. GD3 uptake across the BLM was more efficient than apical delivery. Apical GD3 was metabolized with some cell retention and transfer, whereas basolateral GD3 was mostly metabolized. This study demonstrates efficient GD3 uptake by enterocytes and suggests that the route of delivery influences ganglioside uptake and fate.

apical; brush border membrane; basolateral membrane


Address for reprint requests and other correspondence: M. T. Clandinin, Professor of Nutrition, Alberta Institute for Human Nutrition, 4-10 Agriculture/Forestry Centre, Univ. of Alberta, Edmonton, Alberta, Canada T6G 2P5 (e-mail: tom.clandinin{at}ualberta.ca)






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