@article{e6193f799e07480f9e3b92685d2c1a1f,
title = "Regulation of the metal transporters zip14 and znt10 by manganese intake in mice",
abstract = "The metal transporters ZIP14 and ZnT10 play key physiological roles in maintaining manganese (Mn) homeostasis. However, in vivo regulation of these two transporters by Mn is not understood. Here, we examined how dietary Mn intake regulates ZIP14 and ZnT10 by feeding mice a low-Mn diet, a control diet, or a high-Mn diet for 6 weeks. Inductively coupled plasma mass spectrometry was used to measure Mn and iron (Fe) levels. ZIP14 and ZnT10 protein levels were measured by western blot analysis. While mice on the high-Mn diet exhibited significantly higher levels of Mn in the blood, liver, and brain, the low-Mn diet group did not display matching reductions, indicating that high Mn intake is more effective in disrupting Mn homeostasis in mice. Additionally, Fe levels were only slightly altered, suggesting independent transport mechanisms for Mn and Fe. In the high-Mn diet group, ZIP14 and ZnT10 were both upregulated in the liver, as well as in the small intestine, indicating a coordinated role for these transporters in Mn excretion. Unexpectedly, this upregulation only occurred in male mice, with the exception of hepatic ZIP14, providing new insight into mechanisms behind widely observed sex differences in Mn homeostasis.",
keywords = "Homeostasis, Intestine, Liver, Manganese, Transporters, ZIP14, ZnT10",
author = "Felber, {Danielle M.} and Yuze Wu and Ningning Zhao",
note = "Funding Information: Supplementary Materials: The following are available online at www.mdpi.com/xxx/s1, Figure S1: Metal Levels Figure S1: Metal Levels in Animal Diets. Metal levels measured by inductively coupled plasma mass spectrometry in Animal Diets. Metal levels measured by inductively coupled plasma mass spectrometry (ICP-MS) in AIN-(B9)3FGe pleuvreiflise.d( Can)iZmnall edvieeltss. m(Dod) iCfiuedletvoeclso.ntDaainta 0e.1x pprpemss,e 2d0 apspmme, aonr ±20S0E0 Mpp, mFi gMurne. S(A2:) MAnntilbeovdelys.V(Ber)ifFicea lteivoenl.s. (A()CT) oZcno nlefviremls.t h(De )spCeucilfeicviteylso. fDoautar mexZpIrPe1s4seadntaisbomdeya,nw±e mSEeMas,uFriegduZreIPS124: AexnptribesosdioynVinertihfiecalitvioenrs. (oAf )a Twoilcdotnyfpirem the specificity of our mZIP14 antibody, we measured ZIP14 expression in the livers of a wildtype (WT) mouse, We demonstrated strong signal for the ZIP14 protein in the WT mouse, no signal in the KO mouse, and partial a Zip14 knockout (KO) mouse, and two heterozygous (HZ) mice, using GAPDH as a loading control. We signal in the HZ mice, verifying our anti-mZIP14 antibody. (B) As we do not currently have Znt10 KO mice, we demonstrated strong signal for the ZIP14 protein in the WT mouse, no signal in the KO mouse, and partial signal in the HZ mice, verifying our anti-mZIP14 antibody. (B) As we do not currently have Znt10 KO mice, we ancdonlyfisramteesdw theer espaencailfyiczietyd obfy thimism anutniboobdloyt tbiyn gtr(aInBs)fewcittihnganHtEi-KFL2A93G ceolrlsa wntiit-hm aZnn eTm1p0tayn vtiebcotodri e(Cs.OBNot)h, aβn-dA aC vTeIcNtor encoding mouse ZnT10 (mZnT10) with a FLAG epitope (mZnT10-FLAG). Cells were lysed 48 h after transfection Uncropped Western Blot Images for Figure 6, Figure S5: Uncropped Western Blot Images for Figure 7. and lysates were analyzed by immunoblotting (IB) with anti-FLAG or anti-mZnT10 antibodies. Both β-ACTIN Auanthdo Gr CAoPnDtHrib wuteiroen uss: eCdo ansc elopatudainligz actoionntr,oDls..M, F.Fig.uarned SN3:.ZU.;nmcreotphpoeddolWogeys,teDrn.M B.lFo.ta InmdaNge.Zs.f;ovra Fliidgautrieo nS,2D, F.Mig.uFr.e and N.Z.; formal analysis, D.M.F. and Y.W.; investigation, D.M.F. and Y.W.; resources, N.Z.; data curation, D.M.F.; S4: Uncropped Western Blot Images for Figure 6, Figure S5: Uncropped Western Blot Images for Figure 7. writing—original draft preparation, D.M.F.; writing—review and editing, D.M.F. and N.Z.; supervision, N.Z.; prAojuetchtoardCmoinnitsrtirbautitoionn, Ns: .CZo.;nfucenpdtiunagliazcaqtiuoinsi,t Dio.nM, .NF.. Za.nd N.Z.; methodology, D.M.F. and N.Z.; validation, D.M.F. and N.Z.; formal analysis, D.M.F. and Y.W.; investigation, D.M.F. and Y.W.; resources, N.Z.; data curation, D.M.F.; writing—original draft preparation, D.M.F.; writing—review and editing, D.M.F. and N.Z.; supervision, Acknowledgments: We thank Shannon E. Morgan for critical reading of the manuscript. We thank Mary Kay N.Z.; project administration, N.Z.; funding acquisition, N.Z. Amistadi in the Arizona Laboratory for Emerging Contaminants with the help of ICP-MS measurements. Funding: This work was supported by the National Institutes of Health Grants R00DK104066 (to N.Z.). Publisher Copyright: {\textcopyright} 2019 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2019",
month = sep,
doi = "10.3390/nu11092099",
language = "English (US)",
volume = "11",
journal = "Nutrients",
issn = "2072-6643",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",
}