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Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9

Overbeck, Silke, Uciechowski, Peter, Ackland, M. Leigh, Ford, Dianne and Rink, Lothar 2008, Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9, Journal of leukocyte biology, vol. 83, pp. 368-380, doi: 10.1189/jlb.0307148.

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Title Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9
Author(s) Overbeck, Silke
Uciechowski, Peter
Ackland, M. LeighORCID iD for Ackland, M. Leigh orcid.org/0000-0002-7474-6556
Ford, Dianne
Rink, Lothar
Journal name Journal of leukocyte biology
Volume number 83
Start page 368
End page 380
Total pages 13
Publisher Federation of American Societies for Experimental Biology
Place of publication Bethesda, Md.
Publication date 2008-02
ISSN 0741-5400
Keyword(s) lymphocytes
immunology
trace elements
cation transport protein
humans
Summary Intracellular zinc homeostasis is strictly regulated by zinc binding proteins and zinc transporters. In the present study, we quantified in a first global view the expression of all characterized human zinc exporters (hZnT-1-9) in different leukocyte subsets in response to zinc supplementation and depletion and analyzed their influence on alterations in the intracellular zinc concentration. We found that hZnT-1 is the most regulated zinc exporter. Furthermore, we discovered that hZnT-4 is localized in the plasma membrane similar to hZnT-1. hZnT-4 is most highly expressed in Molt-4, up-regulated after treatment with PHA and is responsible for the measured decrease of intracellular zinc content after high zinc exposure. In addition, we found that hZnT-5, hZnT-6, and hZnT-7 in Raji as well as hZnT-6 and hZnT-7 in THP-1 are up-regulated in response to cellular zinc depletion. Those zinc exporters are all localized in the Golgi network, and this type of regulation explains the observed zinc increase in both cell types after up-regulation of their expression during zinc deficiency and, subsequently, high zinc exposure. Furthermore, we detected, for the first time, the expression of hZnT-8 in peripheral blood lymphocytes, which varied strongly between individuals. While hZnT-2 was not detectable, hZnT-3 and hZnT-9 were expressed at low levels. Further on, the amount of expression was higher in primary cells than in cell lines. These data provide insight into the regulation of intracellular zinc homeostasis in cells of the immune system and may explain the variable effects of zinc deficiency on different leukocyte subsets.
Language eng
DOI 10.1189/jlb.0307148
Field of Research 111601 Cell Physiology
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2008, Federation of American Societies for Experimental Biology
Persistent URL http://hdl.handle.net/10536/DRO/DU:30017266

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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