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Regulation of the Metal Transporters ZIP14 and ZnT10 by Manganese Intake in Mice

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 die...

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Autores principales: Felber, Danielle M., Wu, Yuze, Zhao, Ningning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770778/
https://www.ncbi.nlm.nih.gov/pubmed/31487869
http://dx.doi.org/10.3390/nu11092099
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author Felber, Danielle M.
Wu, Yuze
Zhao, Ningning
author_facet Felber, Danielle M.
Wu, Yuze
Zhao, Ningning
author_sort Felber, Danielle M.
collection PubMed
description 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.
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spelling pubmed-67707782019-10-30 Regulation of the Metal Transporters ZIP14 and ZnT10 by Manganese Intake in Mice Felber, Danielle M. Wu, Yuze Zhao, Ningning Nutrients Article 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. MDPI 2019-09-04 /pmc/articles/PMC6770778/ /pubmed/31487869 http://dx.doi.org/10.3390/nu11092099 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Felber, Danielle M.
Wu, Yuze
Zhao, Ningning
Regulation of the Metal Transporters ZIP14 and ZnT10 by Manganese Intake in Mice
title Regulation of the Metal Transporters ZIP14 and ZnT10 by Manganese Intake in Mice
title_full Regulation of the Metal Transporters ZIP14 and ZnT10 by Manganese Intake in Mice
title_fullStr Regulation of the Metal Transporters ZIP14 and ZnT10 by Manganese Intake in Mice
title_full_unstemmed Regulation of the Metal Transporters ZIP14 and ZnT10 by Manganese Intake in Mice
title_short Regulation of the Metal Transporters ZIP14 and ZnT10 by Manganese Intake in Mice
title_sort regulation of the metal transporters zip14 and znt10 by manganese intake in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770778/
https://www.ncbi.nlm.nih.gov/pubmed/31487869
http://dx.doi.org/10.3390/nu11092099
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