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

CrIII binding to transferrin (Tf; the main FeIII transport protein) has been postulated to mediate cellular uptake of CrIII 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 CrIII binding to vacant FeIII‐binding sites of human Tf effectively blocks cellular CrIII uptake. Through bio‐layer interferometry studies of the Tf cycle, it was found that both exclusion and efflux of Cr2IIITf 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 CrIII is not essential and that Tf binding is likely to be a natural protective mechanism against the toxicity and potential genotoxicity of dietary Cr through blocking CrIII cellular accumulation. You shall not pass: CrIII has been proposed to be an essential trace element and has been postulated to be taken up through binding to the Fe transport protein transferrin (Tf). However, binding of CrIII to vacant FeIII binding sites on transferrin was found to block rather than promote cellular accumulation of CrIII. It thus appears that this process could in fact be a protective mechanism against CrIII toxicity rather than a mechanism of CrIII uptake.