Heme Iron Uptake by Caco-2 Cells is a Saturable, Temperature Sensitive and Modulated by Extracellular pH and Potassium

Abstract

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.

Bioactive Dietary Polyphenols Decrease Heme Iron Absorption by Decreasing Basolateral Iron Release in Human Intestinal Caco-2 Cells

“…HO-1 activity can be increased 10-to 100fold by various conditions, including hyperthermia, heme, and heavy metals such as cobalt and cadmium (36,37). It was suggested that increased HO-1 activity and expression might be responsible for the increased heme iron absorption and a rapid export of heme iron (38,39). Heme iron transport was increased in cells treated with cadmium (38) and the increased heme iron transport was associated with the increased HO-1 protein by heme (39) in Caco-2 cell culture.…”

Cross-Talk Between Body Iron Stores and Diabetes: Iron Stores are Associated with Activity and Microsatellite Polymorphism of the Heme Oxygenase and Type 2 Diabetes

“…The (GT) n repeat was located between the putative heat-shock element and the cis-regulatory element [21] and an increased expression of HO-1 gene may not be beneficial for the host, because HO participates actively in the heme degradation, and the iron released in this reaction could be potentially toxicity for the cell. Also, it must be considered that HO protein expression is increased in cells incubated with increased concentration of inorganic iron [24]. Recent studies have revealed that increased oxidative stress in diabetic rats leads to the induction of HO-1 [25], and it was suggested that the 5′-flanking polymorphism in the HO-1 gene is associated with the development of oxidative stress-mediated diseases, where subjects possessing S/S showed higher expressions of HO-1 mRNA and HO activities [22].…”

Encapsulación de hierro: Otra estrategia para la prevención o tratamiento de la anemia por deficiencia de hierro

“…Esto se conoce con el nombre de liberación controlada (Figura 1D). 7) La encapsulación también permite la posibilidad de mezclar en una misma micro-partícula/micro-cápsula/ liposoma, dos fuentes diferentes de hierro (Figura 1A), ya que el hierro no hemo se absorbe por el transportador de metales divalentes 1 (DMT1), y el hemo mediante la proteína transportadora del grupo hemo 1 (HCP1), y ambos receptores son saturables 1,21 . También con compuestos que promuevan su absorción.…”