Dietary zinc deficiency puts human health at risk, so we explored strategies for enhancing zinc absorption. In the small intestine, the zinc transporter ZIP4 functions as an essential component of zinc absorption. Overexpression of ZIP4 protein increases zinc uptake and thereby cellular zinc levels, suggesting that food components with the ability to increase ZIP4 could potentially enhance zinc absorption via the intestine. In the present study, we used mouse Hepa cells, which regulate mouse Zip4 (mZip4) in a manner indistinguishable from that in intestinal enterocytes, to screen for suitable food components that can increase the abundance of ZIP4. Using this ZIP4-targeting strategy, two such soybean extracts were identified that were specifically able to decrease mZip4 endocytosis in response to zinc. These soybean extracts also effectively increased the abundance of apically localized mZip4 in transfected polarized Caco2 and Madin–Darby canine kidney cells and, moreover, two apically localized mZip4 acrodermatitis enteropathica mutants. Soybean components were purified from one extract and soyasaponin Bb was identified as an active component that increased both mZip4 protein abundance and zinc levels in Hepa cells. Finally, we confirmed that soyasaponin Bb is capable of enhancing cell surface endogenous human ZIP4 in human cells. Our results suggest that ZIP4 targeting may represent a new strategy to improve zinc absorption in humans.
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Research Article|
November 13 2015
Soybean extracts increase cell surface ZIP4 abundance and cellular zinc levels: a potential novel strategy to enhance zinc absorption by ZIP4 targeting
Ayako Hashimoto;
Ayako Hashimoto
*Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
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Katsuma Ohkura;
Katsuma Ohkura
†Department of Bioscience, Fukui Prefectural University, Fukui, Japan
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Masakazu Takahashi;
Masakazu Takahashi
†Department of Bioscience, Fukui Prefectural University, Fukui, Japan
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Kumiko Kizu;
Kumiko Kizu
‡Department of Life and Living, Osaka Seikei College, Osaka, Japan
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Hiroshi Narita;
Hiroshi Narita
§Department of Food Science, Kyoto Women's University, Kyoto, Japan
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Shuichi Enomoto;
Shuichi Enomoto
║Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
¶Center for Molecular Imaging Science, RIKEN Kobe Institute, Kobe, Japan
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Yusaku Miyamae;
Yusaku Miyamae
*Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
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Seiji Masuda;
Seiji Masuda
*Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
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Masaya Nagao;
Masaya Nagao
*Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
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Kazuhiro Irie;
Kazuhiro Irie
**Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, Japan
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Hajime Ohigashi;
Hajime Ohigashi
†Department of Bioscience, Fukui Prefectural University, Fukui, Japan
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Glen K. Andrews;
Glen K. Andrews
††Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS, U.S.A.
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Taiho Kambe
Taiho Kambe
1
*Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
1To whom correspondence should be addressed (email kambe1@kais.kyoto-u.ac.jp).
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Publisher: Portland Press Ltd
Received:
August 05 2015
Revision Received:
September 11 2015
Accepted:
September 17 2015
Accepted Manuscript online:
September 18 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2015 Authors; published by Portland Press Limited
2015
Biochem J (2015) 472 (2): 183–193.
Article history
Received:
August 05 2015
Revision Received:
September 11 2015
Accepted:
September 17 2015
Accepted Manuscript online:
September 18 2015
Citation
Ayako Hashimoto, Katsuma Ohkura, Masakazu Takahashi, Kumiko Kizu, Hiroshi Narita, Shuichi Enomoto, Yusaku Miyamae, Seiji Masuda, Masaya Nagao, Kazuhiro Irie, Hajime Ohigashi, Glen K. Andrews, Taiho Kambe; Soybean extracts increase cell surface ZIP4 abundance and cellular zinc levels: a potential novel strategy to enhance zinc absorption by ZIP4 targeting. Biochem J 1 December 2015; 472 (2): 183–193. doi: https://doi.org/10.1042/BJ20150862
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