% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@PHDTHESIS{Kloubert:742890,
author = {Kloubert, Veronika},
othercontributors = {Rink, Lothar and Slusarenko, A. J.},
title = {{E}influss von {Z}ink auf die {Z}ytokingenregulation},
school = {RWTH Aachen University},
type = {Dissertation},
address = {Aachen},
reportid = {RWTH-2018-228792},
pages = {1 Online-Ressource (IV, 148 Seiten) : Illustrationen},
year = {2018},
note = {Retraction. Aus rechtlichen Gründen kann der Zugriff nicht
gewährt werden.; 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 / 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-2018-228792},
url = {https://publications.rwth-aachen.de/record/742890},
}
guest ::