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Gadolinium-based contrast agents (GBCAs), frequently applied in clinical diagnosis, may cause nephrogenic systemic fibrosis (NSF) probably due to the gadolinium ion (Gd 3+ ) released from the GBCAs. However, Gd-binding proteins and related mechanism responsible for Gd toxicity remained to be understood. In this study, NIH-3T3 cells were chosen as a model for Gd exposure assays and identification of Gd-binding proteins. A comparative assay showed that gadolinium chloride (GdCl 3 ) was much more toxic than gadolinium diamide (Gd-DTPA-BMA, a GBCAs). Majority of Gd were absorbed by cells and existed in the fractions of the cell fragment and soluble proteins. High performance liquid chromatography-inductively coupled plasma mass spectrometry(HPLC-ICP-MS), polyacrylamide gel electrophoresis (SDS PAGE) and liquid chromatography-triple time of flight mass spectrometry (LC-Triple TOF) were employed for the identification and characterization of potential Gd-binging proteins. Tubulin was identified as a novel Gd-binding protein in the NIH-3T3 cells. The binding of Gd to tubulin might inhibit assembling of tubulin or depolymerize microtubules in cells. Our results suggested that the formation of microtubules interfered by binding of free Gd 3+ to tubulin could be an important molecular mechanism of Gd toxicity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Lead (Pb) exposure is well recognized as a significant environmental factor associated with the high incidence of cardiovascular diseases. However, the carriers and molecular targets of Pb in human blood remain to be understood, especially for a real Pb exposure scenario. In this study, a total of 350 blood samples were collected from the smelting workers and systematically analyzed using metallomics and metalloproteomics approaches. The results showed that the majority of Pb (∼99.4%) could be presented in the blood cells. Pb in the cytoplasm of blood cells accounted for approximately 83.1% of the total blood Pb, with nearly half of Pb being bound to proteins. Pb-binding proteins in the blood of workers were identified as hemoglobin, catalase, haptoglobin, δ-aminolevulinic acid dehydratase, and peroxiredoxin-2. Multiple linear regression analysis demonstrated that higher levels of Pb bound to proteins (Mix-bound Pb and Protein-bound Pb) were positively associated with higher systolic blood pressure (p < 0.05). However, the association between blood lead level, Pb levels in the blood cells and systolic blood pressure was not observed (p > 0.05). This study suggested that Pb bound to proteins could be a suitable biomarker for indicating the potential risk of occupational hypertension. [Display omitted] • 99.4% of Pb was concentrated in blood cells of workers, and primarily (83.1%) existed in cytoplasm, the distribution patterns of Pb in the blood was affected by workplaces. • Pb selectively bound to proteins in blood cells of workers, including hemoglobin, catalase, haptoglobin, δ-aminolevulinic acid dehydratase, and peroxiredoxin-2. • Protein-bound Pb is an earlier and more sensitive indicator than blood lead levels, as it is positively correlated with systolic blood pressure, indicating the risk of hypertension. [ABSTRACT FROM AUTHOR]

Fish consumption is one of the major ways through which humans receive exposure to mercury (Hg). The existing forms of Hg in food, particularly Hg bound to proteins, may affect the absorption of Hg by humans and subsequently its potentially toxic effects. However, the knowledge regarding Hg-binding proteins in edible fish muscle is scarce. In the present study, salmon and tuna fish muscles, collected from seven different regions and countries, were analyzed using metallomics- and proteomics-based techniques. The concentration of Hg in sashimi samples ranged from 4.4 to 317.4 ng/g. Size exclusion chromatography (SEC) coupled with inductively coupled plasma mass spectrometer (ICP-MS) showed that beta-actin was a novel Hg-binding protein from the fish muscles, and this protein could also bind bismuth (Bi), silver (Ag), and copper (Cu). Hg bound to beta-actin accounted for approximately 30.2–37.6% of the total Hg in the tuna muscles and was significantly correlated to total Hg in the fish muscles (r = 0.98, p < 0.01) and in the fraction of soluble proteins (r = 0.94, p < 0.01). These findings suggest that proteins act as the main Hg accumulation sites in edible fish; thus, increasing human exposure to Hg following gastrointestinal digestion. • More than half of Hg was deposited in the soluble protein fraction of fish muscle. • Beta-actin was identified as a novel Hg-binding protein in the fish muscle. • More than 30% of the total Hg in tuna muscle was bound to beta-actin. [ABSTRACT FROM AUTHOR]