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

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.

The Combined Effects of Iron Excess in the Diet and Chromium(III) Supplementation on the Iron and Chromium Status in Female Rats

“…The high amount of Fe in the diet might inhibit Cr absorption in the small intestine. Under normal conditions, only about 30% of the potential Fe(III) binding sites in Tf are occupied, leaving the unoccupied binding sites to potentially bind other metal ions [ 8 , 9 , 40 , 41 ]. When the saturation of transferrin with iron rises to over 50%, iron competes with chromium binding, affecting its transport [ 42 ].…”

Stabilities and Biological Activities of Vanadium Drugs: What is the Nature of the Active Species?

“…[18,23] It remains to be established whetherV III -Tf is taken into cells by the same receptormediated endocytosis mechanism as Fe III -Tf (C,S cheme 1), since recent studies showed that aC r III -Tf analog is excluded from cells due to disrupted interactions with the Tf receptor on the cell surface. [28] V V speciesc ause intracellular inhibition of protein tyrosine phosphatases( PTPs), either through reversi-ble binding to Cys residues in the enzymea ctive centers or via strongly oxidizing peroxido vanadates (formedinsitu) that irreversibly oxidize Cys residues to sulfinic acid (Scheme 1). [4,29,30] Both events lead to increased phosphorylation of regulatory proteins to enhance cell signaling, including insulin signaling.…”

Ruthenium(II)–Arene Thiocarboxylates: Identification of a Stable Dimer Selectively Cytotoxic to Invasive Breast Cancer Cells

“…Cellular Ru uptake was measured following our published method . Cell treatments were performed in triplicate in six‐well plates, either by growing MDA‐MB‐231 or A549 cells to ≈80 % confluence and then incubating them with 50 μ m Ru for 4 h (Figure A), or seeding 1.0×10 5 viable cells per well and growing them to near‐confluence for 72 h in the presence of 20 μ m Ru (Figure B).…”