Die Regulation der Zinktransporter und ihr Einfluss auf die intrazelluläre Zinkhomöostase in Leukocyten

Zinc is an essential trace element for the immune system. During this work, important mechanisms regarding the intracellular zinc homeostasis and its influence on intracellular signal transduction in mononuclear cells could be elucidated. The analysis of the expression of zinc exporters, together with the characterisation of zinc importers, has led to the finding that immortal cells maintain their intracellular zinc homeostasis at a lower level due to an overall lower expression of zinc transporters. Under physiological conditions, hZnT-1 was the main transporter in Raji cells and PBMCs, whereas hZnT-5 and hZnT-6 were most highly expressed in THP-1 and Molt-4 cells as well as in purified primary B and T cells, respectively. Furthermore, the regulation of intracellular zinc homeostasis in response to zinc stimulation during zinc deficiency was established. After initial zinc uptake, the zinc concentration in Molt-4 cells decreases due to the newly-discovered membrane-localised hZnT-4, whereas the zinc concentration in Raji and THP-1 cells increases due to the induced elevated expression of the zinc exporters hZnT-5, hZnT-6 and hZnT-7 under zinc depletion. In addition, the up-regulation of hZnT-4 in response to stimulation with PHA illustrates the important function of this zinc exporter for the regulation of the zinc concentration in leukocytes during an activation process. Moreover, the reduced expression of the zinc exporter hZnT-8 in type 1 and type 2 diabetics demonstrates the tremendous significance of this transporter for both diseases. While hZnT-1, hZnT-4, hZnT-5, hZnT-6 and hZnT-7 are fundamental for maintaining zinc homeostasis and thereby associated with the optimal functionality of leukocytes, hZnT-9 as well as hZnT-3 and hZnT-2 seem to play a minor role in the immune system. The influence of zinc on intracellular processes such as apoptosis and the signal transduction induced by interleukins were also characterised in more detail. On the one hand, it could be shown for the first time that an activation of T cells by IL-1beta under zinc deficiency results in increased activity, which correlates with the intracellular zinc concentration. On the other hand, the molecular mechanism for the influence of zinc on the IL-4 signal transduction in T cells could be elucidated. The mechanisms for regulation of intracellular zinc homeostasis and functionality of zinc in cells of the immune system that were established under in vitro conditions provide new therapeutic options for zinc substitution.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2008

Author dc:creator

• Overbeck, Silke

Contributors dc:contributor

• Rink, Lothar

• info:eu-repo/classification/ddc/570
• Zink
• Leukozyt
• Regulation
• Biowissenschaften, Biologie
• Zink-Transporter
• hZnT
• Homoöstase
• zinc
• zinc transporter
• homeostasis
• leukocytes

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-112647%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A50089