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Zinc suppresses hepatic Zip10 expression through activation of MTF‐1
Author(s) -
Lichten Louis A.,
Liuzzi Juan P.,
Cousins Robert J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a170-a
Subject(s) - zinc , zinc deficiency (plant disorder) , intracellular , transcription factor , medicine , endocrinology , messenger rna , gene expression , biology , chemistry , transporter , regulation of gene expression , microbiology and biotechnology , gene , biochemistry , organic chemistry
The Zip transporter family acts to increase the intracellular zinc concentration. The mechanisms of regulation are largely unknown. Recently, hepatic Zip10 expression was shown to increase in vivo in the absence of metal‐responsive transcription factor‐1 (MTF‐1). The aim of the current study was to determine if zinc and/or nitric oxide (NO) could regulate hepatic Zip10 , and if this regulation occurs via MTF‐1. First, CD‐1 mice were fed a zinc‐deficient diet (<1 ppm) for 21 d. In agreement with a regulatory role for MTF‐1, hepatic Zip10 mRNA and protein expression were increased with dietary zinc restriction. We next investigated the effects of supplemental zinc by incubating AML12 hepatocytes with increasing amounts of zinc (0–100 μM) for 24 h. In this case, a dose‐dependent decrease in Zip10 mRNA expression was observed, with an approximate 10‐fold decrease within 3 h after zinc addition. Similar results were observed with NO. The mechanism for the apparent negative regulation of Zip10 by zinc and/or NO was elucidated by using MTF‐1 siRNA in AML12 hepatocytes. Neither zinc nor NO could suppress Zip10 expression in the absence of MTF‐1. These results suggest that hepatic Zip10 expression is negatively regulated by zinc through MTF‐1, and Zip10 may be important for maintaining hepatic zinc levels during deficiency. Supported by NIH grant DK31127 and Boston Family Endowment funds (RJC) and CALS Alumni Fellowship (LAL).