Binding of Chromium(III) to Transferrin Could Be Involved in Detoxification of Dietary Chromium(III) Rather than Transport of an Essential Trace Element

摘要

Cr-III binding to transferrin (Tf; the main Fe-III transport protein) has been postulated to mediate cellular uptake of Cr-III to facilitate a purported essential role for this element. Experiments using HepG2 (human hepatoma) cells, which were chosen because of high levels of the transferrin receptor, showed that Cr-III binding to vacant Fe-III-binding sites of human Tf effectively blocks cellular Cr-III uptake. Through bio-layer interferometry studies of the Tf cycle, it was found that both exclusion and efflux of (Cr2Tf)-Tf-III from cells was caused by 1) relatively low Cr2Tf affinity to cell-surface Tf receptors compared to Fe2Tf, and 2) disruption of metal release under endosomal conditions and post-endosomal Tf dissociation from the receptor. These data support mounting evidence that Cr-III is not essential and that Tf binding is likely to be a natural protective mechanism against the toxicity and potential geno-toxicity of dietary Cr through blocking Cr-III cellular accumulation.