Channels, transporters and receptors for cadmium and cadmium complexes in eukaryotic cells: myths and facts

Thévenod, Frank; Fels, Johannes; Lee, Wing-Kee; Zarbock, Ralf

doi:10.1007/s10534-019-00176-6

Cited by 63 publications

(58 citation statements)

References 179 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cadmium (Cd 2+ ) is a xenobiotic which is known to induce alteration of gene expression (Chen et al 2019;Rani et al 2014). Cd 2+ enters into the cells through numerous transporters including TRPM7 (Thevenod et al 2019). TRPM7 is for instance involved in Cd 2+ entry in HEK293 expressing TRPM7 (Monteilh-Zoller et al 2003) and in human osteoclasts (Martineau et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Cadmium exposure enhances cell migration and invasion through modulated TRPM7 channel expression

et al. 2020

View full text Add to dashboard Cite

Cadmium is a xenobiotic involved in neoplastic transformation. Cadmium enters the cells through divalent cation transporters including the Transient Receptor Potential Melastatin-related 7 (TRPM7) which is known to be involved in cancer cell fate. This work aimed to study the role of TRPM7 in neoplastic transformation induced by cadmium exposure in non-cancer epithelial cells. Non-cancer epithelial cells were chronically exposed to low-dose of cadmium. TRPM7 expression and function were studied by Western-Blot, Patch-Clamp and calcium and magnesium imaging. Finally, cell migration and invasion were studied by Boyden chamber assays. Chronic cadmium exposure induced TRPM7 overexpression and increased the membrane currents (P < 0.001). Cells exposed to cadmium had higher intracellular calcium and magnesium levels (P < 0.05). TRPM7 silencing restored calcium levels but strongly decreased intracellular magnesium concentration (P < 0.001). Moreover, cadmium exposure enhanced both cell migration and invasion, but TRPM7 silencing strongly decreased these features (P < 0.001). Furthermore, mammary epithelial cells exposed to cadmium became rounded and had less cell-to-cell junctions. Cadmium exposure decreased epithelial markers while the mesenchymal ones were increased. Importantly, TRPM7 silencing was able to reverse these phenotypic modifications (P < 0.05). To summarize, our data show that chronic cadmium exposure enhanced TRPM7 expression and activity in non-cancer epithelial cells. TRPM7 overexpression induced intracellular magnesium increase and stimulated cell migration and invasion. These neoplastic properties could be linked to a TRPM7dependent epithelial-to-mesenchymal transition reprogramming in cell exposed to cadmium. These findings provide new insights into the regulation of cell fates by cadmium exposure. Keywords Cadmium • TRPM7 • Magnesium • Cell invasion • EMT Abbreviations BCA Bicinchoninic acid Ca 2+ Calcium Cd 2+ Cadmium DMEM/F-12 Dulbecco's modified Eagle's medium/ nutrient mixture F-12 DMSO Dimethyl sulfoxide EDTA Ethylenediaminetetraacetic acid EGTA Ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetraacetic acid EMT Epithelial-to-mesenchymal transition ER Estrogen receptor FCS Fetal calf serum Mg 2+ Magnesium Mn 2+ Manganese MIC Magnesium inhibited cation MTT 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide SDS Sodium dodecyl sulfate siControl Scrambled small interfering RNA Electronic supplementary material The online version of this article (

show abstract

Section: Discussionmentioning

confidence: 99%

Cadmium exposure enhances cell migration and invasion through modulated TRPM7 channel expression

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In addition, Cd 2+ may bind to the amino acidcystine transporters (SLC79/SLC3A1 and SLC7A9/SLC7A13) to access the cytosol. Besides, it is accepted that Cd 2+ has direct interaction with cellular DNA, is capable of inhibiting the nuclease of incision during DNA repair, as well as be able to exert an interference in the chromatin condensation [36].…”

Section: Discussionmentioning

confidence: 99%

CdCl2 has zero-order kinetic cellular influx and induces cytotoxicity and genotoxicity at low concentrations in human leukocytes in vitro

Santos

Serpa

Silva

et al. 2019

Rev. Colomb. Cienc. Quím. Farm.

View full text Add to dashboard Cite

Cadmium (Cd2+) is a nonessential heavy metal that possesses a high capacity of bioaccumulation and exhibits toxic characteristics even at low concentrations. This study evaluated the genotoxicity and cytotoxicity in human leukocytes in vitro after exposure to a lower range of Cd2+concentration (1-25 μg/mL) using an unprecedented strategy by correlating between intracellular Cd2+ levels after exposure and cellular damage. Results demonstrated that Cd2+exposure from 5 to 25 μg/mL significantly increased the unviability of leukocytes, as well as the DNA damage, which was dose-dependent. The intracellular Cd2+ levels in leukocytes ranged from 9.85 to 94.38 pg/cell, and cytotoxicity and genotoxicity were induced at a concentration of 24.22 pg/cell. The relationship between exposure concentration and intracellular Cd2+ levels suggests that its influx occurs in human leukocytes under zeroorder kinetics.

show abstract

“…Cd in plasma is filterable by glomeruli if it is bound to GSH, amino acids, MT, or PC [8,9], but the fraction of circulating Cd that enters the filtrate is unknown. The proximal tubule reabsorbs and retains most or all of the filtered Cd with an array of channels, solute carriers, and mediators of endocytosis [7,10,[13][14][15][16]. Basolateral uptake may also add to the cellular content of Cd in the proximal tubule [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

The Source and Pathophysiologic Significance of Excreted Cadmium

Satarug

Vesey

Ruangyuttikarn

et al. 2019

Toxics

View full text Add to dashboard Cite

In theory, the identification of the source of excreted cadmium (Cd) might elucidate the pathogenesis of Cd-induced chronic kidney disease (CKD). With that possibility in mind, we studied Thai subjects with low, moderate, and high Cd exposure. We measured urine concentrations of Cd, ([Cd]u); N-acetyl-β-d-glucosaminidase, a marker of cellular damage ([NAG]u); and β2-microglobulin, an indicator of reabsorptive dysfunction ([β2MG]u). To relate excretion rates of these substances to existing nephron mass, we normalized the rates to creatinine clearance, an approximation of the glomerular filtration rate (GFR) (ECd/Ccr, ENAG/Ccr, and Eβ2MG/Ccr). To link the loss of intact nephrons to Cd-induced tubular injury, we examined linear and quadratic regressions of estimated GFR (eGFR) on ECd/Ccr, eGFR on ENAG/Ccr, and ENAG/Ccr on ECd/Ccr. Estimated GFR varied inversely with both ratios, and ENAG/Ccr varied directly with ECd/Ccr. Linear and quadratic regressions of Eβ2MG/Ccr on ECd/Ccr and ENAG/Ccr were significant in moderate and high Cd-exposure groups. The association of ENAG/Ccr with ECd/Ccr implies that both ratios depicted cellular damage per surviving nephron. Consequently, we infer that excreted Cd emanated from injured tubular cells, and we attribute the reduction of eGFR to the injury. We suggest that ECd/Ccr, ENAG/Ccr, and eGFR were associated with one another because each parameter was determined by the tubular burden of Cd.

show abstract

Channels, transporters and receptors for cadmium and cadmium complexes in eukaryotic cells: myths and facts

Cited by 63 publications

References 179 publications

Cadmium exposure enhances cell migration and invasion through modulated TRPM7 channel expression

Cadmium exposure enhances cell migration and invasion through modulated TRPM7 channel expression

CdCl2 has zero-order kinetic cellular influx and induces cytotoxicity and genotoxicity at low concentrations in human leukocytes in vitro

The Source and Pathophysiologic Significance of Excreted Cadmium

Contact Info

Product

Resources

About