Soybean extracts increase cell surface ZIP4 abundance and cellular zinc levels: A potential novel strategy to enhance zinc absorption by ZIP4 targeting

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 bothmZip4 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 targetingmay represent a new strategy to improve zinc absorption in humans.

Original languageEnglish
Pages (from-to)183-193
Number of pages11
JournalBiochemical Journal
Volume472
Issue number2
DOIs
Publication statusPublished - Dec 1 2015

Keywords

  • Apical membrane
  • Degradation
  • Endocytosis
  • Screening
  • Soyasaponin Bb
  • Zinc transporter

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Hashimoto, A., Ohkura, K., Takahashi, M., Kizu, K., Narita, H., Enomoto, S., Miyamae, Y., Masuda, S., Nagao, M., Irie, K., Ohigashi, H., Andrews, G. K., & Kambe, T. (2015). Soybean extracts increase cell surface ZIP4 abundance and cellular zinc levels: A potential novel strategy to enhance zinc absorption by ZIP4 targeting. Biochemical Journal, 472(2), 183-193. https://doi.org/10.1042/BJ20150862