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Title: Zinc deficiency causes delayed ATP clearance and adenosine generation in rats and cell culture models
Authors: Takeda, Taka-aki
Miyazaki, Shiho
Kobayashi, Miki
Nishino, Katsutoshi  kyouindb  KAKEN_id
Goto, Tomoko
Matsunaga, Mayu
Ooi, Minami
Shirakawa, Hitoshi
Tani, Fumito  kyouindb  KAKEN_id
Kawamura, Tatsuyoshi
Komai, Michio
Kambe, Taiho  kyouindb  KAKEN_id
Author's alias: 西野, 勝俊
谷, 史人
神戸, 大朋
Issue Date: 22-Aug-2018
Publisher: Springer Science and Business Media LLC
Journal title: Communications Biology
Volume: 1
Thesis number: 113
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.
Rights: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI(Published Version): 10.1038/s42003-018-0118-3
PubMed ID: 30271993
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