Enhanced cadmium-induced testicular necrosis and renal proximal tubule damage caused by gene-dose increase in a <i>Slc39a8</i>-transgenic mouse line

Wang, Bin; Schneider, Scott N.; Dragin, Nadine; Girijashanker, Kuppuswami; Dalton, Timothy P.; He, Lei; Miller, Marian L.; Stringer, Keith; Soleimani, Manoocher; Richardson, Douglas D.; Nebert, Daniel W.

doi:10.1152/ajpcell.00409.2006

Cited by 103 publications

(115 citation statements)

References 42 publications

Supporting

Mentioning

107

Contrasting

Order By: Relevance

“…3, right). Northern blot analysis of untreated C57BL/6J mice (Wang et al, 2007) agrees with the present Q-PCR data. We have also found that mouse yolk sac and placenta contain substantial levels of both ZIP14 and ZIP8 mRNA (B. Wang and D. W. Nebert, manuscript in preparation).…”

Section: Discussionsupporting

confidence: 90%

“…Recent studies have shown such a relationship: allelic differences in the mouse Slc39a8 gene are responsible for striking variability in risk of Cd 2ϩ -induced testicular necrosis among different inbred mouse strains (Dalton et al, 2005), as well as Cd 2ϩ -induced acute renal failure (Wang et al, 2007). Slc39a8 encodes the ZIP8 transporter, which undoubtedly also transports an essential divalent cation.…”

mentioning

confidence: 99%

“…Although Mn 2ϩ was shown to be the best inhibitor of ZIP8-mediated Cd 2ϩ uptake and has a very low K m value for ZIP8-mediated uptake (2.2 M) (He et al, 2006), we believe that zinc (Zn 2ϩ ) cannot be ruled out as a substrate for ZIP8. Indeed, in studies with X. laevis oocytes (Liu et al, 2008) (He et al, 2006;Wang et al, 2007).…”

mentioning

confidence: 99%

“…ZIP8 is localized on apical surfaces (He et al, 2006) of several cell types: between the blood and vascular endothelial cells of the testis (Dalton et al, 2005;Wang et al, 2007), and between the glomerular filtrate and proximal tubular epithelial cells of the kidney (Wang et al, 2007). ZIP8 therefore seems to act as a "gatekeeper" for maintaining intracellular Zn 2ϩ and perhaps Mn 2ϩ homeostasis.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Slc39a14 Gene Encodes ZIP14, A Metal/Bicarbonate Symporter: Similarities to the ZIP8 Transporter

et al. 2008

Self Cite

View full text Add to dashboard Cite

The mouse and human genomes contain 14 highly conserved SLC39 genes. Viewed from an evolutionary perspective, SLC39A14 and SLC39A8 are the most closely related, each having three noncoding exons 1. However, SLC39A14 has two exons 4, giving rise to Zrt-and Irt-related protein (ZIP)ZIP14A and ZIP14B alternatively spliced products. C57BL/6J mouse ZIP14A expression is highest in liver, duodenum, kidney, and testis; ZIP14B expression is highest in liver, duodenum, brain, and testis; and ZIP8 is highest in lung, testis, and kidney. We studied ZIP14 stably retroviral-infected mouse fetal fibroblast cultures and transiently transfected Madin-Darby canine kidney (MDCK) polarized epithelial cells. Our findings include: 1) ZIP14-mediated cadmium uptake is proportional to cell toxicity, but

show abstract

Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Slc39a14 Gene Encodes ZIP14, A Metal/Bicarbonate Symporter: Similarities to the ZIP8 Transporter

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…Fourteen members of the ZIP (Zrt, Irt-related protein) family encoded by SLC39A genes play a role in increasing cytosolic Zn, whereas the ZnT family members encoded by SLC30A play a role in decreasing cytosolic Zn (Kambe, 2011). Among these Zn transporters, ZIP8 and ZIP14 encoded by SLC39A8 and SLC39A14, respectively, have been shown to be involved in cellular Cd transport (Dalton et al, 2005;He et al, 2006;Wang et al, 2007;Yanagiya et al, 2000;Fujishiro et al, 2006). ZIP8 and ZIP14 have affinities for Cd 2+ and Mn 2+ in addition to Zn 2+ (Girijashanker et al, 2008;He et al, 2006;Himeno et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Concentration-dependent roles of DMT1 and ZIP14 in cadmium absorption in Caco-2 cells

et al. 2017

View full text Add to dashboard Cite

-Intestinal absorption of cadmium (Cd) is considered to be mediated mainly by the ferrous iron transporter DMT1, or the calcium transporter CaT1. The roles of zinc transporters such as ZIP8 and ZIP14 remain unclear, and the roles of these four transporters in the intestinal uptake of Cd under physiological conditions have not been compared. Here, we used a trans-well cell culture system to investigate the effects of the down-regulation of these four transporters on the uptake of Cd from the apical side of enterocytes. We used a Caco-2-kh cell line that can form tight junctions within a few days. The transfection of DMT1 siRNA significantly decreased the Cd uptake from the apical side at 5 μM, but not at 0.1 or 1 μM. The transfection of ZIP14 siRNA markedly decreased the Cd uptake at 0.1 and 1 μM, but not at 5 μM. The transfection of siRNA of CaT1 or ZIP8 did not alter the Cd uptake at any concentrations of Cd examined. These results suggest that DMT1 and ZIP14 play different roles in intestinal Cd absorption depending on the concentration of Cd.

show abstract

The role of ZIP8 down‐regulation in cadmium‐resistant metallothionein‐null cells

Fujishiro

Okugaki

Kubota

et al. 2009

J of Applied Toxicology

View full text Add to dashboard Cite

The mechanisms of cellular cadmium uptake in mammalian cells remain obscure. To solve this problem, we established cadmium-resistant cells (A7 and B5) from metallothionein-null mouse cells, and found that cadmium accumulation was markedly suppressed in these cells. DNA microarray and real-time PCR analyses revealed that expressions of ZIP (Zrt-, Irt-related protein) 8 and ZIP14 were down-regulated in A7 and B5 cells. In particular, both mRNA and protein levels of ZIP8 were markedly suppressed in A7 and B5 cells. Introduction of short hairpin RNA (shRNA) of ZIP8 into parental cells reduced the accumulation of cadmium to about 35% of that of mock-transfected cells, whereas the introduction of shRNA of divalent metal transporter 1 hardly changed cadmium accumulation. Thus, the cadmium resistance in A7 and B5 cells may be conferred primarily by the down-regulation of ZIP8. In mouse tissues, high expression of ZIP8 was noted in the liver, kidney, lung and testis. These data suggest that ZIP8 plays an important role in cellular uptake of cadmium.

show abstract

Enhanced cadmium-induced testicular necrosis and renal proximal tubule damage caused by gene-dose increase in a Slc39a8-transgenic mouse line

Cited by 103 publications

References 42 publications

Slc39a14 Gene Encodes ZIP14, A Metal/Bicarbonate Symporter: Similarities to the ZIP8 Transporter

Slc39a14 Gene Encodes ZIP14, A Metal/Bicarbonate Symporter: Similarities to the ZIP8 Transporter

Concentration-dependent roles of DMT1 and ZIP14 in cadmium absorption in Caco-2 cells

The role of ZIP8 down‐regulation in cadmium‐resistant metallothionein‐null cells

Contact Info

Product

Resources

About