Tissue-specific induction of mouse ZIP8 and ZIP14 divalent cation/bicarbonate symporters by, and cytokine response to, inflammatory signals

Marina Gálvez-Peralta, Zhifang Wang, Shengying Bao, Daren L Knoell, Daniel W. Nebert

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Mouse Slc39a8 and Slc39a14 genes encode ZIP8 and ZIP14, respectively, which are ubiquitous divalent cation/(HCO3-)2 symporters responsible for uptake of Zn2+, Fe2+, and Mn2+ into cells. Cd2+ and other toxic nonessential metals can displace essential cations, thereby entering vertebrate cells. Whereas Slc39a8 encodes a single protein, Slc39a14 has 2 exons 4 which, via alternative splicing, give rise to ZIP14A and ZIP14B; why differences exist in cell type-specific expression of ZIP14A and ZIP14B remains unknown. Inflammatory stimuli have been associated with upregulation of ZIP8 and ZIP14, but a systematic study of many tissues simultaneously in a laboratory animal following inflammatory cytokine exposure has not yet been reported. Herein, we show that C57BL/6J male mice - treated intraperitoneally with lipopolysaccharide or the proinflammatory cytokines tumor necrosis factor (TNF) or interleukin-6 (IL6) - exhibited quantatively very different, highly tissue-specific, and markedly time-dependent up- and downregulation of ZIP8, ZIP14A, and ZIP14B messenger RNA (mRNA) levels in 12 tissues. The magnitude of inflammatory response was confirmed by measuring the proinflammatory cytokine TNF, IL6, and interleukin-1Î mRNA levels in the same tissues of these animals. Our data suggest that most if not all tissues use ZIP8, ZIP14A, and/or ZIP14B for Zn2+ uptake, some tissues under basal conditions and others moreso when inflammatory stressors are present; collectively, this might lead to substantial alterations in plasma Zn2+ levels due to Zn2+ redistribution not just in liver but across many vital organs. In the context of cadmium-mediated toxicity, our data suggest that tissues other than liver, kidney, and lung should also be considered.

Original languageEnglish (US)
Pages (from-to)246-258
Number of pages13
JournalInternational Journal of Toxicology
Volume33
Issue number3
DOIs
StatePublished - Jan 1 2014

Fingerprint

Symporters
Divalent Cations
Bicarbonates
Tissue
Cytokines
Liver
Interleukin-6
Animals
Up-Regulation
Tumor Necrosis Factor-alpha
Messenger RNA
Poisons
Alternative Splicing
Laboratory Animals
Cadmium
Interleukin-1
Toxicity
Lipopolysaccharides
Vertebrates
Cations

Keywords

  • ZIP transporter gene family
  • inflammation
  • interleukin-6
  • lipopolysaccharide
  • mouse Slc39 gene family
  • tumor necrosis factor

ASJC Scopus subject areas

  • Toxicology

Cite this

Tissue-specific induction of mouse ZIP8 and ZIP14 divalent cation/bicarbonate symporters by, and cytokine response to, inflammatory signals. / Gálvez-Peralta, Marina; Wang, Zhifang; Bao, Shengying; Knoell, Daren L; Nebert, Daniel W.

In: International Journal of Toxicology, Vol. 33, No. 3, 01.01.2014, p. 246-258.

Research output: Contribution to journalArticle

@article{d44bbac120d1401984f1d1558a76ac4d,
title = "Tissue-specific induction of mouse ZIP8 and ZIP14 divalent cation/bicarbonate symporters by, and cytokine response to, inflammatory signals",
abstract = "Mouse Slc39a8 and Slc39a14 genes encode ZIP8 and ZIP14, respectively, which are ubiquitous divalent cation/(HCO3-)2 symporters responsible for uptake of Zn2+, Fe2+, and Mn2+ into cells. Cd2+ and other toxic nonessential metals can displace essential cations, thereby entering vertebrate cells. Whereas Slc39a8 encodes a single protein, Slc39a14 has 2 exons 4 which, via alternative splicing, give rise to ZIP14A and ZIP14B; why differences exist in cell type-specific expression of ZIP14A and ZIP14B remains unknown. Inflammatory stimuli have been associated with upregulation of ZIP8 and ZIP14, but a systematic study of many tissues simultaneously in a laboratory animal following inflammatory cytokine exposure has not yet been reported. Herein, we show that C57BL/6J male mice - treated intraperitoneally with lipopolysaccharide or the proinflammatory cytokines tumor necrosis factor (TNF) or interleukin-6 (IL6) - exhibited quantatively very different, highly tissue-specific, and markedly time-dependent up- and downregulation of ZIP8, ZIP14A, and ZIP14B messenger RNA (mRNA) levels in 12 tissues. The magnitude of inflammatory response was confirmed by measuring the proinflammatory cytokine TNF, IL6, and interleukin-1{\^I} mRNA levels in the same tissues of these animals. Our data suggest that most if not all tissues use ZIP8, ZIP14A, and/or ZIP14B for Zn2+ uptake, some tissues under basal conditions and others moreso when inflammatory stressors are present; collectively, this might lead to substantial alterations in plasma Zn2+ levels due to Zn2+ redistribution not just in liver but across many vital organs. In the context of cadmium-mediated toxicity, our data suggest that tissues other than liver, kidney, and lung should also be considered.",
keywords = "ZIP transporter gene family, inflammation, interleukin-6, lipopolysaccharide, mouse Slc39 gene family, tumor necrosis factor",
author = "Marina G{\'a}lvez-Peralta and Zhifang Wang and Shengying Bao and Knoell, {Daren L} and Nebert, {Daniel W.}",
year = "2014",
month = "1",
day = "1",
doi = "10.1177/1091581814529310",
language = "English (US)",
volume = "33",
pages = "246--258",
journal = "International Journal of Toxicology",
issn = "1091-5818",
publisher = "SAGE Publications Inc.",
number = "3",

}

TY - JOUR

T1 - Tissue-specific induction of mouse ZIP8 and ZIP14 divalent cation/bicarbonate symporters by, and cytokine response to, inflammatory signals

AU - Gálvez-Peralta, Marina

AU - Wang, Zhifang

AU - Bao, Shengying

AU - Knoell, Daren L

AU - Nebert, Daniel W.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Mouse Slc39a8 and Slc39a14 genes encode ZIP8 and ZIP14, respectively, which are ubiquitous divalent cation/(HCO3-)2 symporters responsible for uptake of Zn2+, Fe2+, and Mn2+ into cells. Cd2+ and other toxic nonessential metals can displace essential cations, thereby entering vertebrate cells. Whereas Slc39a8 encodes a single protein, Slc39a14 has 2 exons 4 which, via alternative splicing, give rise to ZIP14A and ZIP14B; why differences exist in cell type-specific expression of ZIP14A and ZIP14B remains unknown. Inflammatory stimuli have been associated with upregulation of ZIP8 and ZIP14, but a systematic study of many tissues simultaneously in a laboratory animal following inflammatory cytokine exposure has not yet been reported. Herein, we show that C57BL/6J male mice - treated intraperitoneally with lipopolysaccharide or the proinflammatory cytokines tumor necrosis factor (TNF) or interleukin-6 (IL6) - exhibited quantatively very different, highly tissue-specific, and markedly time-dependent up- and downregulation of ZIP8, ZIP14A, and ZIP14B messenger RNA (mRNA) levels in 12 tissues. The magnitude of inflammatory response was confirmed by measuring the proinflammatory cytokine TNF, IL6, and interleukin-1Î mRNA levels in the same tissues of these animals. Our data suggest that most if not all tissues use ZIP8, ZIP14A, and/or ZIP14B for Zn2+ uptake, some tissues under basal conditions and others moreso when inflammatory stressors are present; collectively, this might lead to substantial alterations in plasma Zn2+ levels due to Zn2+ redistribution not just in liver but across many vital organs. In the context of cadmium-mediated toxicity, our data suggest that tissues other than liver, kidney, and lung should also be considered.

AB - Mouse Slc39a8 and Slc39a14 genes encode ZIP8 and ZIP14, respectively, which are ubiquitous divalent cation/(HCO3-)2 symporters responsible for uptake of Zn2+, Fe2+, and Mn2+ into cells. Cd2+ and other toxic nonessential metals can displace essential cations, thereby entering vertebrate cells. Whereas Slc39a8 encodes a single protein, Slc39a14 has 2 exons 4 which, via alternative splicing, give rise to ZIP14A and ZIP14B; why differences exist in cell type-specific expression of ZIP14A and ZIP14B remains unknown. Inflammatory stimuli have been associated with upregulation of ZIP8 and ZIP14, but a systematic study of many tissues simultaneously in a laboratory animal following inflammatory cytokine exposure has not yet been reported. Herein, we show that C57BL/6J male mice - treated intraperitoneally with lipopolysaccharide or the proinflammatory cytokines tumor necrosis factor (TNF) or interleukin-6 (IL6) - exhibited quantatively very different, highly tissue-specific, and markedly time-dependent up- and downregulation of ZIP8, ZIP14A, and ZIP14B messenger RNA (mRNA) levels in 12 tissues. The magnitude of inflammatory response was confirmed by measuring the proinflammatory cytokine TNF, IL6, and interleukin-1Î mRNA levels in the same tissues of these animals. Our data suggest that most if not all tissues use ZIP8, ZIP14A, and/or ZIP14B for Zn2+ uptake, some tissues under basal conditions and others moreso when inflammatory stressors are present; collectively, this might lead to substantial alterations in plasma Zn2+ levels due to Zn2+ redistribution not just in liver but across many vital organs. In the context of cadmium-mediated toxicity, our data suggest that tissues other than liver, kidney, and lung should also be considered.

KW - ZIP transporter gene family

KW - inflammation

KW - interleukin-6

KW - lipopolysaccharide

KW - mouse Slc39 gene family

KW - tumor necrosis factor

UR - http://www.scopus.com/inward/record.url?scp=84901045911&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901045911&partnerID=8YFLogxK

U2 - 10.1177/1091581814529310

DO - 10.1177/1091581814529310

M3 - Article

VL - 33

SP - 246

EP - 258

JO - International Journal of Toxicology

JF - International Journal of Toxicology

SN - 1091-5818

IS - 3

ER -