Abstract
The investigation of luminal factors influencing zinc availability and accessibility in the intestine is of great interest when analyzing parameters regulating intestinal zinc resorption. Of note, intestinal mucins were suggested to play a beneficial role in the luminal availability of zinc. Their exact zinc binding properties, however, remain unknown and the impact of these glycoproteins on human intestinal zinc resorption has not been investigated in detail. Thus, the aim of this study is to elucidate the impact of intestinal mucins on luminal uptake of zinc into enterocytes and its transfer into the blood. In the present study, in vitro zinc binding properties of mucins were analyzed using commercially available porcine mucins and secreted mucins of the goblet cell line HT-29-MTX. The molecular zinc binding capacity and average zinc binding affinity of these glycoproteins demonstrates that mucins contain multiple zinc-binding sites with biologically relevant affinity within one mucin molecule. Zinc uptake into the enterocyte cell line Caco-2 was impaired by zinc-depleted mucins. Yet this does not represent their form in the intestinal lumen in vivo under zinc adequate conditions. In fact, zinc-uptake studies into enterocytes in the presence of mucins with differing degree of zinc saturation revealed zinc buffering by these glycoproteins, indicating that mucin-bound zinc is still available for the cells. Finally, the impact of mucins on zinc resorption using three-dimensional cultures was studied comparing the zinc transfer of a Caco-2/HT-29-MTX co-culture and conventional Caco-2 monoculture. Here, the mucin secreting co-cultures yielded higher fractional zinc resorption and elevated zinc transport rates, suggesting that intestinal mucins facilitate the zinc uptake into enterocytes and act as a zinc delivery system for the intestinal epithelium.
Highlights
The essential trace element zinc is predominantly resorbed in the small intestine, where it is absorbed by enterocytes and transported into the blood stream, primarily mediated by the apically located Zrt, Irt-like transporter (ZIP)-4 and the basolateral zinc exporter (ZnT)-1 [1]
While the impact of mucins for iron resorption was investigated in detail, there is evidence that the mucus layer might be important for zinc uptake by the human intestinal mucosa, as zinc binding by mucins was observed in animal studies [4,5,9,10]
By clarifying the molecular zinc binding capacity of these glycoproteins and their average affinity for the bivalent cation, we could demonstrate that mucins bind multiple zinc ions with physiologically relevant affinity
Summary
The essential trace element zinc is predominantly resorbed in the small intestine, where it is absorbed by enterocytes and transported into the blood stream, primarily mediated by the apically located Zrt-, Irt-like transporter (ZIP)-4 and the basolateral zinc exporter (ZnT)-1 [1]. While the impact of mucins for iron resorption was investigated in detail, there is evidence that the mucus layer might be important for zinc uptake by the human intestinal mucosa, as zinc binding by mucins was observed in animal studies [4,5,9,10]. The detailed role of the intestinal mucus on human zinc absorption has not yet been investigated
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