Mammalian Zinc Transporters

Liuzzi, Juan P.; Cousins, Robert J.

doi:10.1146/annurev.nutr.24.012003.132402

Cited by 513 publications

(410 citation statements)

References 108 publications

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“…Second, associations between the BMI-increasing allele of rs13107325 in SLC39A8 with both metabolically 'unhealthy' (lower HDL-cholesterol) and metabolically 'healthy' (lower diastolic BP) phenotypes confirm findings from GWASs for BP and blood lipids [32][33][34]. The BMI-associated variant rs13107325 is a non-synonymous SNP located in exon 7 [34] of the SLC39A8 gene, which encodes a zinc transporter involved in zinc transportation into the cell at the onset of inflammation [35,36]. As indicated recently, zinc deficiency is also associated with lower BP [37].…”

Section: Discussionsupporting

confidence: 54%

Pleiotropic effects of obesity-susceptibility loci on metabolic traits: a meta-analysis of up to 37,874 individuals

et al. 2013

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Aims/hypothesis Genetic pleiotropy may contribute to the clustering of obesity and metabolic conditions. We assessed whether genetic variants that are robustly associated with BMI and waist-to-hip ratio (WHR) also influence metabolic and cardiovascular traits, independently of obesity-related traits, in meta-analyses of up to 37,874 individuals from six European population-based studies. Methods We examined associations of 32 BMI and 14 WHR loci, individually and combined in two genetic predisposition scores (GPSs), with glycaemic traits, blood lipids and BP, with and without adjusting for BMI and/or WHR. Results We observed significant associations of BMIincreasing alleles at five BMI loci with lower levels of 2 h glucose (RBJ [also known as DNAJC27], QPTCL: effect sizes −0.068 and −0.107 SD, respectively), HDL-cholesterol (SLC39A8: −0.065 SD, MTCH2: −0.039 SD), and diastolic BP (SLC39A8: −0.069 SD), and higher and lower levels of LDL-and total cholesterol (QPTCL: 0.041 and 0.042 SDs, respectively, FLJ35779 [also known as POC5]: −0.042 and −0.041 SDs, respectively) (all p<2.4×10 −4 ), independent of BMI. The WHR-increasing alleles at two WHR loci were significantly associated with higher proinsulin (GRB14: 0.069 SD) and lower fasting glucose levels (CPEB4: −0.049 SD), independent of BMI and WHR. A higher GPS-BMI was associated with lower systolic BP (−0.005 SD), diastolic BP (−0.006 SD) and 2 h glucose (−0.013 SD), while a higher GPS-WHR was associated with lower HDL-cholesterol Electronic supplementary material The online version of this article (doi:10.1007/s00125-013-2985-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users. J. V. van Vliet-Ostaptchouk : M. M. van der Klauw :

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Section: Discussionsupporting

confidence: 54%

Pleiotropic effects of obesity-susceptibility loci on metabolic traits: a meta-analysis of up to 37,874 individuals

et al. 2013

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“…Common variables summarised in Table 1 (age, height and weight) also did not exert effects on gene expression in our sample. SLC30A8, a member of the zinc transporter family, has previously been detected primarily in the secretory vesicles of beta cells [8] with reports of lower expression levels in other tissues including the liver [9]. A novel finding in the present study was that immunohistochemical staining localised SLC30A8 in the liver, albeit not in hepatic parenchyma, but in nuclei of the sinusoidal fat-storing cells.…”

Section: Discussionsupporting

confidence: 65%

Expression analysis of loci associated with type 2 diabetes in human tissues

et al. 2010

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Aims/hypothesis Genetic mapping has identified over 20 loci contributing to genetic risk of type 2 diabetes. The next step is to identify the genes and mechanisms regulating the contributions of genetic risk to disease. The goal of this study was to evaluate the effect of age, height, weight and risk alleles on expression of candidate genes in diabetesassociated regions in three relevant human tissues. Methods We measured transcript abundance for WFS1, KCNJ11, TCF2 (also known as HNF1B), PPARG, HHEX, IDE, CDKAL1, CDKN2A, CDKN2B, IGF2BP2, SLC30A8 and TCF7L2 by quantitative RT-PCR in human pancreas (n=50), colon (n=195) and liver (n=50). Tissue samples were genotyped for single nucleotide polymorphisms (SNPs) associated with type 2 diabetes. The effects of age, height, weight, tissue and SNP on RNA expression were tested by linear modelling. Results Expression of all genes exhibited tissue bias. Immunohistochemistry confirmed the findings for HHEX, IDE and SLC30A8, which showed strongest tissue-specific mRNA expression bias. Neither age, height nor weight were associated with gene expression. We found no evidence that type 2 diabetes-associated SNPs affect neighbouring gene expression (cis-expression quantitative trait loci) in colon, pancreas and liver. Conclusions/interpretation This study provides new evidence that tissue-type, but not age, height, weight or SNPs in or near candidate genes associated with increased risk of type 2 diabetes are strong contributors to differential gene expression in the genes and tissues examined.Electronic supplementary material The online version of this article

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“…Zip proteins have been shown to import zinc into the cytosol from the plasma membrane or intracellular organelles (3,4). The Zip superfamily name stands for Zrt-and Irt-like proteins.…”

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confidence: 99%

“…For example, Arabidopsis Irt2 transports iron and zinc (9), and ZupT from Escherichia coli transports iron, zinc, cobalt, and possibly manganese (10). To date, the predominant substrates of mammalian Zip proteins are largely unknown (3,4). This background prompted us to investigate a role for Zip14 in iron transport.…”

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confidence: 99%

Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells

Liuzzi

Aydemir

Nam

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Zip14 is a member of the SLC39A zinc transporter family, which is involved in zinc uptake by cells. Up-regulation of Zip14 by IL-6 appears to contribute to the hepatic zinc accumulation and hypozincemia of inflammation. At least three members of the SLC39A family transport other trace elements, such as iron and manganese, in addition to zinc. We analyzed the capability of Zip14 to mediate non-transferrin-bound iron (NTBI) uptake by overexpressing mouse Zip14 in HEK 293H cells and Sf9 insect cells. Zip14 was found to localize to the plasma membrane, and its overexpression increased the uptake of both 65 Zn and 59 Fe. Addition of bathophenanthroline sulfonate, a cell-impermeant ferrous iron chelator, inhibited Zip14-mediated iron uptake from ferric citrate, suggesting that iron is taken up by HEK cells as Fe 2؉ . Iron uptake by HEK and Sf9 cells expressing Zip14 was inhibited by zinc. Suppression of endogenous Zip14 expression by using Zip14 siRNA reduced the uptake of both iron and zinc by AML12 mouse hepatocytes. Zip14 siRNA treatment also decreased metallothionein mRNA levels, suggesting that compensatory mechanisms were not sufficient to restore intracellular zinc. Collectively, these results indicate that Zip14 can mediate the uptake of zinc and NTBI into cells and that it may play a role in zinc and iron metabolism in hepatocytes, where this transporter is abundantly expressed. Because NTBI is commonly found in plasma of patients with hemochromatosis and transfusional iron overload, Zip14-mediated NTBI uptake may contribute to the hepatic iron loading that characterizes these diseases.hemochromatosis ͉ iron transport ͉ liver ͉ zinc transport ͉ inflammation

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Mammalian Zinc Transporters

Cited by 513 publications

References 108 publications

Pleiotropic effects of obesity-susceptibility loci on metabolic traits: a meta-analysis of up to 37,874 individuals

Pleiotropic effects of obesity-susceptibility loci on metabolic traits: a meta-analysis of up to 37,874 individuals

Expression analysis of loci associated with type 2 diabetes in human tissues

Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells

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