Heme iron uptake by Caco-2 cells is a saturable, temperature sensitive and modulated by extracellular pH and potassium.
It is known that heme iron and inorganic iron are absorbed differently. Heme iron is found in the diet mainly in the form of hemoglobin and myoglobin. The mechanism of iron absorption remains uncertain. This study focused on the heme iron uptake by Caco-2 cells from a hemoglobin digest and its response to different iron concentrations. We studied the intracellular Fe concentration and the effect of time, K+ depletion, and cytosol acidification on apical uptake and transepithelial transport in cells incubated with different heme Fe concentrations. Cells incubated with hemoglobin-digest showed a lower intracellular Fe concentration than cells grown with inorganic Fe. However, uptake and transepithelial transport of Fe was higher in cells incubated with heme Fe. Heme Fe uptake had a low Vmax and Km as compared to inorganic Fe uptake and did not compete with non-heme Fe uptake. Heme Fe uptake was inhibited in cells exposed to K+ depletion or cytosol acidification. Heme oxygenase 1 expression increased and DMT1 expression decreased with higher heme Fe concentrations in the media. The uptake of heme iron is a saturable and temperature-dependent process and, therefore, could occur through a mechanism involving both a receptor and the endocytic pathway.
Arredondo
Miguel
M
Laboratorio de Micronutrientes, INTA, Universidad de Chile, Casilla 138-11, Santiago, Chile. marredon@inta.cl
Kloosterman
Janneke
J
Núñez
Sergio
S
Segovia
Fabián
F
Candia
Valeria
V
Flores
Sebastián
S
Le Blanc
Solange
S
Olivares
Manuel
M
Pizarro
Fernando
F
D018938:Caco-2 Cells; D027682:Cation Transport Proteins / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D011188:Potassium / Q000494:pharmacology*; D013696:Temperature; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D006418:Heme; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D007501:Iron; D011188:Potassium; D000099236:Solute Carrier Family 11, Member 2; C496541:HMOX1 protein, human; C105245:heme oxygenase-2