Roles of Zinc Transporters That Control the Essentiality and Toxicity of Manganese and Cadmium

• Himeno Seiichiro

  Faculty of Pharmaceutical Sciences, Tokushima Bunri University

• Fujishiro Hitomi

  Faculty of Pharmaceutical Sciences, Tokushima Bunri University

Bibliographic Information

Other Title

• マンガン，カドミウムの必須性・毒性を左右する亜鉛輸送体の役割
• Symposium Review マンガン,カドミウムの必須性・毒性を左右する亜鉛輸送体の役割
• Symposium Review マンガン,カドミウム ノ ヒッスセイ ・ ドクセイ オ サユウ スル アエン ユソウタイ ノ ヤクワリ

Abstract

Cellular transport systems for both essential and toxic trace elements remain elusive. In our studies on the transport systems for cadmium (Cd), we found that the cellular uptake of Cd is mediated by the transporter for manganese (Mn). We identified ZIP8 and ZIP14, members of the ZIP zinc (Zn) transporter family, as transporters having high affinities for both Cd and Mn. Notably, the uptake of Cd into rice root from soil is mediated by a transporter for Mn as well. We found that ZIP8 is highly expressed at the S3 segment of the kidney proximal tubule and can transport glomerulus-filtered Cd and Mn ions in the lumen into epithelial cells of the proximal tubule, suggesting that ZIP8 has an important role in the renal reabsorption of both toxic Cd and essential Mn. Mutations in ZIP8 and ZIP14 genes were found in humans having congenital disorders associated with the disturbed transport of Mn, although ZIP8 mutation causes whole-body Mn deficiency while ZIP14 mutation causes Mn accumulation in the brain. Mutations in ZnT10, a Zn transporter responsible for Mn excretion, also cause hyperaccumulation of Mn in the brain. Results of genome-wide association studies have indicated that ZIP8 SNPs are involved in a variety of common diseases. Thus, ZIP8, ZIP14, and ZnT10 play crucial roles in the transport of Mn and thereby control Mn- and Cd-related biological events in the body.

Journal

• YAKUGAKU ZASSHI

  YAKUGAKU ZASSHI 141 (5), 695-703, 2021-05-01

  The Pharmaceutical Society of Japan

Keywords

• manganese
• cadmium
• zinc
• transporter
• kidney

Details

• CRID: 1390006432292988928
• NII Article ID: 130008032754
• NII Book ID: AN00284903
• DOI: 10.1248/yakushi.20-00243-5
• ISSN: 13475231
• ISSN: 00316903
• NDL BIB ID: 031499118
• PubMed: 33952754
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I031499118
• Web Site: https://www.jstage.jst.go.jp/article/yakushi/141/5/141_20-00243-5/_pdf
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed