Zinc deficiency causes delayed ATP clearance and adenosine generation in rats and cell culture models

• Takeda, Taka-aki

  Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University

• Miyazaki, Shiho

  Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University

• Kobayashi, Miki

  Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University

• Nishino, Katsutoshi

  Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University

• Goto, Tomoko

  Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University･Faculty of Human Life Science, Miyagi Gakuin Women‘s University

• Matsunaga, Mayu

  Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University

• Ooi, Minami

  Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University

• Shirakawa, Hitoshi

  Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University

• Tani, Fumito

  Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University

• Kawamura, Tatsuyoshi

  Department of Dermatology, Faculty of Medicine, University of Yamanashi

• Komai, Michio

  Department of Science of Food Function and Health, Graduate School of Agricultural Science, Tohoku University

• Kambe, Taiho

  Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University

Abstract

Zinc deficiency causes myriad pathophysiological symptoms, but why distinct phenotypes are generated by zinc deficiency remains unclear. Considering that several ectoenzymes involved in purinergic signaling through extracellular adenine-nucleotide hydrolysis possess zinc ions in their active sites, and disorders in purinergic signaling result in diverse diseases that are frequently similar to those caused by zinc deficiency, herein we examine whether zinc deficiency affects extracellular adenine-nucleotide metabolism. Zinc deficiency severely impairs the activities of major ectoenzymes (ENPP1, ENPP3, NT5E/CD73, and TNAP), and also strongly suppresses adenine-nucleotide hydrolysis in cell-membrane preparations or rat plasma, thereby increasing ATP and ADP levels and decreasing adenosine levels. Thus, zinc deficiency delays both extracellular ATP clearance and adenosine generation, and zinc modulates extracellular adenine-nucleotide metabolism. Since the finely tuned balance between extracellular adenine nucleotides and adenosine is critical for purinergic signaling, these findings provide a novel insight into why zinc deficiency results in diverse symptoms.

Journal

• Communications Biology

  Communications Biology 1 113-, 2018-08-22

  Springer Science and Business Media LLC

Keywords

• General Agricultural and Biological Sciences
• General Biochemistry, Genetics and Molecular Biology
• Medicine (miscellaneous)

Details

• CRID: 1050845763804817280
• NII Article ID: 120006766123
• ISSN: 23993642
• DOI: 10.1038/s42003-018-0118-3
• HANDLE: 2433/244792
• Web Site: https://www.nature.com/articles/s42003-018-0118-3.pdf
• Web Site: https://www.nature.com/articles/s42003-018-0118-3
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN