Physiologically relevant plasma d , l -homocysteine concentrations mobilize Cd from human serum albumin

Sagmeister, Peter; Gibson, Matthew; McDade, Kyle H.; Gailer, Jürgen

doi:10.1016/j.jchromb.2016.05.014

Cited by 14 publications

(9 citation statements)

References 59 publications

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“…The Cd that remains in the plasma is bound to the amino acid histidine and proteins such as MT, pre-albumin, albumin, α 2 -macroglobulin, and immunoglobulins G and A [126,158,159]. A range of low molecular weight thiols, including GSH, cysteine, cysteinylglycine, homocysteine, and γ-glutamylcysteine, are also possible carriers of Cd [160][161][162]. The total concentrations of these low molecular weight thiols are in the low µM range (12-20 µM), while albumin thiol is more abundant (~0.6 mM).…”

Section: Cadmium In Erythrocytes Versus Blood Plasma (Serum)mentioning

confidence: 99%

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Satarug

Gobé

Vesey

et al. 2020

Toxics

127

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The present review aims to provide an update on health risks associated with the low-to-moderate levels of environmental cadmium (Cd) and lead (Pb) to which most populations are exposed. Epidemiological studies examining the adverse effects of coexposure to Cd and Pb have shown that Pb may enhance the nephrotoxicity of Cd and vice versa. Herein, the existing tolerable intake levels of Cd and Pb are discussed together with the conventional urinary Cd threshold limit of 5.24 μg/g creatinine. Dietary sources of Cd and Pb and the intake levels reported for average consumers in the U.S., Spain, Korea, Germany and China are summarized. The utility of urine, whole blood, plasma/serum, and erythrocytes to quantify exposure levels of Cd and Pb are discussed. Epidemiological studies that linked one of these measurements to risks of chronic kidney disease (CKD) and mortality from common ailments are reviewed. A Cd intake level of 23.2 μg/day, which is less than half the safe intake stated by the guidelines, may increase the risk of CKD by 73%, and urinary Cd levels one-tenth of the threshold limit, defined by excessive ß2-microglobulin excretion, were associated with increased risk of CKD, mortality from heart disease, cancer of any site and Alzheimer’s disease. These findings indicate that the current tolerable intake of Cd and the conventional urinary Cd threshold limit do not provide adequate health protection. Any excessive Cd excretion is probably indicative of tubular injury. In light of the evolving realization of the interaction between Cd and Pb, actions to minimize environmental exposure to these toxic metals are imperative.

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Section: Cadmium In Erythrocytes Versus Blood Plasma (Serum)mentioning

confidence: 99%

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Satarug

Gobé

Vesey

et al. 2020

Toxics

127

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“…We investigated the effect of physiologically relevant Cys and hCys concentrations dissolved in the PBS-buffer mobile phase on the stability of an HSA/Hg/Cd complex [ 13 , 36 , 37 ]. It is important to utilize PBS buffer in the execution of these studies because this buffer closely resembles the chemical composition of human blood plasma and therefore precludes the generation of artefacts, which have been observed when plasma metalloproteins were previously analyzed using different biochemical buffers [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

More Effective Mobilization of Hg2+ from Human Serum Albumin Compared to Cd2+ by L-Cysteine at Near-Physiological Conditions

Gautam

Gailer

2023

Toxics

Self Cite

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Although chronic low-level exposure to Hg2+ and Cd2+ causes human nephrotoxicity, the bioinorganic processes that deliver them to their target organs are poorly understood. Since the plasma protein human serum albumin (HSA) has distinct binding sites for these metal ions, we wanted to gain insight into these translocation processes and have employed size-exclusion chromatography coupled on-line to an inductively coupled plasma atomic emission spectrometer using phosphate-buffered saline mobile phases. When HSA ‘labeled’ with Hg2+ and Cd2+ (1:0.1:0.1) using 300 μM of L-methionine was analyzed, the co-elution of a single C, S, Cd, and Hg peak was observed, which implied the intact bis-metalated HSA complex. Since human plasma contains small molecular weight thiols and sulfur-containing metabolites, we analyzed the bis-metalated HSA complex with mobile phases containing 50–200 µM of L-cysteine (Cys), D,L-homocysteine (hCys), or glutathione (GSH), which provided insight into the comparative mobilization of each metal from their respective binding sites on HSA. Interestingly, 50 µM Cys, hCys, or GSH mobilized Hg2+ from its HSA binding site but only partially mobilized Cd2+ from its binding site. Since these findings were obtained at conditions simulating near-physiological conditions of plasma, they provide a feasible explanation for the higher ‘mobility’ of Hg2+ and its concomitant interaction with mammalian target organs compared to Cd2+. Furthermore, 50 µM Cys resulted in the co-elution of similar-sized Hg and Cd species, which provides a biomolecular explanation for the nephrotoxicity of Hg2+ and Cd2+.

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“…Less than 10% of Cd the circulation is in the plasma, where it is associated with histidine and thiols (-SH) of peptides and proteins, such as pre-albumin, albumin, α 2 -macroglobulin, and immunoglobulins G and A [ 74 , 77 , 78 ]. Examples of the non-protein plasma thiols that interact with Cd are glutathione (GSH), cysteine, cysteinylglycine, homocysteine, and γ-glutamylcysteine [ 79 , 80 ]. The total concentrations of these non-protein thiols are in the low µM range (12–20 µM).…”

Section: Exposure Sources Dosimetry and Health Risk Assessmentmentioning

confidence: 99%

Is Environmental Cadmium Exposure Causally Related to Diabetes and Obesity?

Satarug

2023

Cells

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Cadmium (Cd) is a pervasive toxic metal, present in most food types, cigarette smoke, and air. Most cells in the body will assimilate Cd, as its charge and ionic radius are similar to the essential metals, iron, zinc, and calcium (Fe, Zn, and Ca). Cd preferentially accumulates in the proximal tubular epithelium of the kidney, and is excreted in urine when these cells die. Thus, excretion of Cd reflects renal accumulation (body burden) and the current toxicity of Cd. The kidney is the only organ other than liver that produces and releases glucose into the circulation. Also, the kidney is responsible for filtration and the re-absorption of glucose. Cd is the least recognized diabetogenic substance although research performed in the 1980s demonstrated the diabetogenic effects of chronic oral Cd administration in neonatal rats. Approximately 10% of the global population are now living with diabetes and over 80% of these are overweight or obese. This association has fueled an intense search for any exogenous chemicals and lifestyle factors that could induce excessive weight gain. However, whilst epidemiological studies have clearly linked diabetes to Cd exposure, this appears to be independent of adiposity. This review highlights Cd exposure sources and levels associated with diabetes type 2 and the mechanisms by which Cd disrupts glucose metabolism. Special emphasis is on roles of the liver and kidney, and cellular stress responses and defenses, involving heme oxygenase-1 and -2 (HO-1 and HO-2). From heme degradation, both HO-1 and HO-2 release Fe, carbon monoxide, and a precursor substrate for producing a potent antioxidant, bilirubin. HO-2 appears to have also anti-diabetic and anti-obese actions. In old age, HO-2 deficient mice display a symptomatic spectrum of human diabetes, including hyperglycemia, insulin resistance, increased fat deposition, and hypertension.

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Physiologically relevant plasma d , l -homocysteine concentrations mobilize Cd from human serum albumin

Cited by 14 publications

References 59 publications

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

Cadmium and Lead Exposure, Nephrotoxicity, and Mortality

More Effective Mobilization of Hg2+ from Human Serum Albumin Compared to Cd2+ by L-Cysteine at Near-Physiological Conditions

Is Environmental Cadmium Exposure Causally Related to Diabetes and Obesity?

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