Cooperation of metallothionein and zinc transporters for regulating zinc homeostasis in human intestinal Caco-2 cells

Shen, Hui; Qin, Haihong; Guo, Junsheng

doi:10.1016/j.nutres.2008.02.011

Cited by 36 publications

(34 citation statements)

References 39 publications

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“…1). Despite previous reports that TPEN modulates expression of zinc transporter proteins (Devergnas et al 2004;Shen et al 2008), we found no change in the expression of ZnT-1, ZnT-3, or SYP in TPEN-treated mouse brains (Fig. 2).…”

Section: Discussioncontrasting

confidence: 99%

Endogenous Zinc Mediates Apoptotic Programmed Cell Death in the Developing Brain

et al. 2009

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Endogenous zinc can mediate the apoptotic programmed cell death (PCD) in the developing brain. Intensive accumulation of labile zinc occurs in almost all neurons undergoing PCD in the developing rat brain. Based on the greater frequency of neurons with intensive zinc accumulation compared to apoptotic neurons, it is inferred that cytosolic zinc accumulation precedes apoptotic PCD. To determine the role of intracellular labile zinc in developmental apoptosis, we subcutaneously injected the membrane-permeant zinc chelator, N,N,N',N-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) into postnatal rats for 7 days after birth. TPEN chelated intraneuronal zinc without modulating the expression of the zinc-regulating proteins, ZnT-1, ZnT-3, and synaptophysin. The frequency of apoptotic neurons significantly decreased in TPEN-treated rat brains compared with that in normal postnatal rats. Activating cleavages of caspase-9 and -3, and mitochondrial pro-apoptotic Bax expression were reduced, whereas expression of anti-apoptotic Bcl-2 was increased. Thus, intracerebral zinc chelation may arrest PCD in the developing brain by interfering with the caspase-dependent apoptotic pathway. The present study demonstrates that intracellular zinc acts as a key mediator of developmental apoptosis and therefore provides the first in vivo evidence that endogenous labile zinc causes neuronal apoptosis.

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Section: Discussioncontrasting

confidence: 99%

Endogenous Zinc Mediates Apoptotic Programmed Cell Death in the Developing Brain

et al. 2009

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“…The present study found a reduction of DMT-1 mRNA expression after addition of TPEN, but its increase with the nano-ZnO and ZnSO 4 supplementation. This result is in agreement with Shen et al (2008), who reported that mRNA expression of DMT-1 is susceptible to low zinc concentration and resistant to TPEN treatment (Stark 2011). But the transporting mechanism of zinc regulated by DMT-1 has not been investigated yet, thus more detailed exploration is needed.…”

Section: Discussionsupporting

confidence: 92%

“…In the current study, IEC-6 cell was used as a model to assess the effect of nano-ZnO, ZnO, ZnSO 4 , and TPEN on cell viability, zinc uptake efficiency, and zinc transporters gene expression. The cell viability inhibition by TPEN has already been suggested (Shen et al 2008). Furthermore, a more recent study reported that TPEN addition noticeably lowered cell viability in HT-29 cells (Gurusamy et al 2011).…”

Section: Discussionmentioning

confidence: 77%

“…But as a consequence of its rapid absorption characteristics, most of the studies showed cytotoxicity of nano-ZnO because of particle dissolution and zinc release in the medium or uptake in the cells leading to cell injury (Xia et al 2008;De Berardis et al 2010). In this regard, many recent reports have confirmed that nano-ZnO has adverse biological outcomes on the prokaryotic and eukaryotic system, while in an appropriate concentration it is nontoxic to natural biomolecules (Hanley et al 2008;Shen et al 2008). A majority of those studies have focused on some low tolerance cells, including immune cells, or even on some immortalized cells lines, which showed changed sensitivities to some chemicals by altering metabolic processes of cells.…”

Section: Doi: 1017221/15/2016-cjasmentioning

confidence: 99%

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Effect of ZnO nanoparticle on cell viability, zinc uptake efficiency, and zinc transporters gene expression: a comparison with ZnO and ZnSO<sub>4</sub>

Zhang¹,

Wang²,

Mao³

et al. 2017

CZECH J ANIM SCI

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Zhang X., Wang Z., Mao L., Dong X., Peng Q., Chen J., Tan C., Hu R. (2017): Effect of ZnO nanoparticle on cell viability, zinc uptake efficiency, and zinc transporters gene expression: a comparison with ZnO and ZnSO 4 . Czech J. Anim. Sci., 62, 32-41.Zinc plays an important role in functional and structural integrity of cells. The aim of the current study was to compare cell viability, zinc uptake efficiency, and gene expression of metallothionein (MT), divalent metal transporter (DMT-1), and other important zinc transporters (ZnTs) under experimental treatment of TPEN (N, N, N', N'-Tetrakis (2-pyridylmethyl) ethylenediamine) (2 µM), and three zinc sources (zinc oxide nanoparticle (nano-ZnO), bulk zinc oxide (ZnO), and zinc sulfate (ZnSO 4 )) at different levels (25, 50, and 100 µM) in rat intestinal epithelial cell line IEC-6. Cells were classified into TPEN group and TPEN + zinc sources groups. In the present study, significantly decreased cell viability was observed in TPEN group, while supplementations with nano-ZnO at all levels and ZnO (50 and 100 µM) significantly increased the cell viability. ZnSO 4 at a high concentration (100 µM) inhibited cell viability. Furthermore, cells of nano-ZnO group showed the highest viability at a 25 µM concentration. The uptake efficiency of nano-ZnO is higher than that of ZnSO 4 and ZnO. Additionally, a significant down-regulation for ZnT-1, ZnT-4, MT, DMT-1 mRNA with TPEN treatment was detected. Compared with the unchanged ZnT-4, all zinc treatments up-regulated the gene expressions of ZnT-1, MT, Our results indicate that nano-ZnO is more effective than ZnO and ZnSO 4 in enhancing cell viability, and its lower cytotoxicity, higher uptake efficiency, and comparative transportation at low concentration also favour its potential use as a new zinc source in feed additives.

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“…Because the sole Zn transporter known to be expressed at the basolateral membrane of the enterocyte and the Caco-2 cells, i.e., ZnT1 belonging to the SLC30 family, mediates cellular Zn efflux (McMahon and Cousins. 1998;Shen et al 2008), we do not suspect that the inhibitory effect of Zn reveals the involvement of some Zn mechanisms of transport in the basolateral uptake of Cd. However, the possibility that ZnT1 could mediate uptake processes under some experimental conditions with the metal gradient favoring influx deserves to be investigated in future studies.…”

Section: Variation In Transport Properties As a Function Of Metal Spementioning

confidence: 79%

Characterization of basolateral-to-apical transepithelial transport of cadmium in intestinal TC7 cell monolayers

et al. 2011

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Cadmium (Cd) is a toxic metal with an extremely long half-life in humans. The intestinal absorption of Cd has been extensively studied but the role the intestinal epithelium may play in metal excretion has never been considered. The basolateral (BL)-to-apical (AP) transepithelial transport of Cd was characterized in TC7 human intestinal cells. Both AP and BL uptakes varied with days in culture, and BL uptake was twofold higher compared to AP in differentiated cultures. A 50% increase in the BL uptake of 0.5 μM (109)Cd was observed at pH 8.5 in a chloride but not nitrate medium, suggesting the involvement of a pH-sensitive mechanism of transport for chloro-complexes. Fe and Zn inhibited the BL uptake of Cd whereas complexation by albumin had no effect, but the stimulatory effect of pH 8.5 was lost in the presence of albumin. The BL uptake of [(3)H]-MPP(+) and (109)Cd were both inhibited by decynium22 without reciprocal inhibition. MRP2 and MDR1 mRNA levels increased as a function of days in culture. A 25 and 20% decrease in the cellular AP efflux of Cd was observed in the presence of verapamil and probenecid, respectively. In cells treated with BSO, which lowered by 26% the total cellular thiol content, the inhibitory effect of verapamil increased, whereas that of probenecid decreased. These results reveal the existence of a decynium22-sensitive mechanism of transport for Cd at the BL membrane, and suggest the involvement of MDR1 and MRP2 in cellular Cd efflux at the AP membrane. It is conceivable that the intestinal epithelium may contribute to Cd blood excretion.

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Cooperation of metallothionein and zinc transporters for regulating zinc homeostasis in human intestinal Caco-2 cells

Cited by 36 publications

References 39 publications

Endogenous Zinc Mediates Apoptotic Programmed Cell Death in the Developing Brain

Endogenous Zinc Mediates Apoptotic Programmed Cell Death in the Developing Brain

Effect of ZnO nanoparticle on cell viability, zinc uptake efficiency, and zinc transporters gene expression: a comparison with ZnO and ZnSO<sub>4</sub>

Characterization of basolateral-to-apical transepithelial transport of cadmium in intestinal TC7 cell monolayers

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