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@PHDTHESIS{Kloubert:992673,
      author       = {Kloubert, Veronika},
      othercontributors = {Rink, Lothar and Slusarenko, A. J.},
      title        = {{E}influss von {Z}ink auf die {Z}ytokingenregulation;
                      [korrigierte {A}uflage]},
      school       = {RWTH Aachen University},
      type         = {Dissertation},
      address      = {Aachen},
      publisher    = {RWTH Aachen University},
      reportid     = {RWTH-2024-08345},
      pages        = {1 Online-Ressource (IV, 147 Seiten) : Illustrationen},
      year         = {2018},
      note         = {Korrigierte Auflage. - Veröffentlicht auf dem
                      Publikationsserver der RWTH Aachen University 2024;
                      Dissertation, RWTH Aachen University, 2018},
      abstract     = {Zinc deficiency in T cells is associated with decreased
                      interleukin (IL)-2 production. The underlying molecular
                      mechanisms leading to reduced IL-2 production are so far not
                      completely elucidated. Here, a new molecular link,
                      connecting zinc deficiency with decreased IL-2 production in
                      T cells, was identified. This link is presented by the
                      transcription factor cAMP responsive element modulator
                      (CREM)α. After zinc deficiency, CREMα expression is
                      increased on RNA and protein levels. An association between
                      zinc, IL-2 and CREMα was confirmed in vitro as well as in
                      vivo. In vivo, increased IL-2 production was associated with
                      decreased CREMα production upon zinc supplementation of
                      pigs. It is likely that increased amounts of CREMα in T
                      cells, caused by increased protein phosphatase (PP)2A
                      activity, lead to enhanced recruitment of histone
                      deacetylase (HDAC)1. Here, it was shown that zinc leads to
                      inhibited HDAC1 activity. Under zinc deficiency, HDAC1 is
                      more active, which in turn causes increased histone
                      deacetylation, resulting in a more condensed DNA state
                      followed by reduced transcription. The half-maximal
                      concentration of zinc on HDAC1 was determined with a value
                      of 0.26 nM, correlating the intracellular amount of zinc in
                      zinc adequate Jurkat cells. Moreover, zinc deficiency caused
                      increased deacetylation of H3K9. Proper zinc homeostasis is
                      ensured by regulation of zinc transporters. Here,
                      significant up-regulation of Zip10 expression was observed
                      in contrast to significant down-regulation of ZnT1, ZnT3 and
                      ZnT8 transporter expression. Participation of the
                      transcription factor metal-responsive transcription factor
                      (MTF)-1 as an additional regulator of IL-2 expression could
                      be excluded as well as differential methylation of the IL2
                      gene after zinc deficiency. To summarize, a molecular link
                      was found with CREMα, connecting zinc with altered IL-2
                      production in T cells. One possible future approach might be
                      to beneficially influence impaired IL-2 production due to
                      zinc supplementation, ensuring proper immune responses.
                      Apart from that, the use of zinc as an HDAC1 inhibitor might
                      be applied in different illnesses.},
      cin          = {525501-2 ; 924820 / 161510 / 160000},
      ddc          = {570},
      cid          = {$I:(DE-82)525501-2_20140620$ / $I:(DE-82)161510_20140620$ /
                      $I:(DE-82)160000_20140620$},
      typ          = {PUB:(DE-HGF)11},
      doi          = {10.18154/RWTH-2024-08345},
      url          = {https://publications.rwth-aachen.de/record/992673},
}