Uptake and fate of ganglioside GD3 in human intestinal Caco-2 cells.
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.
Schnabl
Kareena L
KL
Department of Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta T6G 2P5, Canada.
Larcelet
Marjorie
M
Thomson
Alan B R
AB
Clandinin
Michael T
MT
D001692:Biological Transport; D001711:Biotransformation; D018938:Caco-2 Cells; D016764:Cell Polarity; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005732:Gangliosides / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D009336:Necrosis
D005732:Gangliosides; C026226:ganglioside, GD3