Submitted on October 16, 2008
Revised on April 8, 2009
Accepted on May 4, 2009
Uptake and fate of ganglioside GD3 in human intestinal CaCo-2 cells
Kareena L Schnabl1, Marjorie Larcelet2, Alan B. R. Thomson1, and Michael Tom Clandinin1*
1 University of Alberta
2 École nationale supérieure de biologie appliquée à la nutrition et à l'alimentation (ENSBANA)
* To whom correspondence should be addressed. E-mail: tclandin{at}ualberta.ca.
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 has 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, while 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.
