Binding of Chromium(III) to Transferrin Could Be Involved in Detoxification of Dietary Chromium(III) Rather than Transport of an Essential Trace Element. Issue 28 (20th May 2016)

• Record Type: Journal Article
• Authors: Levina, Aviva; Pham, T. H. Nguyen; Lay, Peter A.
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 28(2016)
• Page Start: 8104
• Page End: 8107
• Publication Date: 2016-05-20
• Subjects: chromium -- metal homeostasis -- toxicity -- trace elements -- transferrin; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201602996
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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 Cr2 III Tf from cells was caused by 1) relatively low Cr2 Tf affinity to cell‐surface Tf receptors compared to Fe2 Tf, 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 genotoxicity of dietary Cr through blocking Cr III cellular accumulation. Abstract : You shall not pass : Cr III 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 Cr III to vacant Fe III binding sites on transferrin was found to block rather than promote cellular accumulation of Cr III . It thus appears that this process could in fact be a protective mechanism against Cr III toxicity rather than a mechanism of Cr III uptake.