Intracellular zinc homeostasis in leukocyte subsets is regulated by different expression of zinc exporters ZnT-1 to ZnT-9.
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.
Overbeck
Silke
S
Institute of Immunology, RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52074 Aachen, Germany.
Uciechowski
Peter
P
Ackland
M Leigh
ML
Ford
Dianne
D
Rink
Lothar
L
D027682:Cation Transport Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006056:Golgi Apparatus / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007962:Leukocytes / Q000145:classification / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors; D015032:Zinc / Q000378:metabolism* / Q000494:pharmacology; D000075703:Zinc Transporter 8
D027682:Cation Transport Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C498299:SLC30A1 protein, human; C486299:SLC30A2 protein, human; C102806:SLC30A3 protein, human; C491597:SLC30A4 protein, human; C457225:SLC30A5 protein, human; C504822:SLC30A6 protein, human; C472294:SLC30A7 protein, human; C492522:SLC30A8 protein, human; C120900:SLC30A9 protein, human; D014157:Transcription Factors; D000075703:Zinc Transporter 8; D015032:Zinc