@article{SpeckmannSchulzHilleretal.2017,
  author    = {Speckmann, Bodo and Schulz, Sarah and Hiller, Franziska and Hesse, Deike and Schumacher, Fabian and Kleuser, Burkhard and Geisel, Juergen and Obeid, Rima and Grune, Tilman and Kipp, Anna Patricia},
  title     = {Selenium increases hepatic DNA methylation and modulates one-carbon metabolism in the liver of mice},
  series = {The journal of nutritional biochemistry},
  volume    = {48},
  journal   = {The journal of nutritional biochemistry},
  publisher = {Elsevier},
  address   = {New York},
  issn      = {0955-2863},
  doi       = {10.1016/j.jnutbio.2017.07.002},
  pages     = {112 -- 119},
  year      = {2017},
  abstract  = {The average intake of the essential trace element selenium (Se) is below the recommendation in most European countries, possibly causing sub-optimal expression of selenoproteins. It is still unclear how a suboptimal Se status may affect health. To mimic this situation, mice were fed one of three physiologically relevant amounts of Se. We focused on the liver, the organ most sensitive to changes in the Se supply indicated by hepatic glutathione peroxidase activity. In addition, liver is the main organ for synthesis of methyl groups and glutathione via one-carbon metabolism. Accordingly, the impact of Se on global DNA methylation, methylation capacity, and gene expression was assessed. We observed higher global DNA methylation indicated by LINE1 methylation, and an increase of the methylation potential as indicated by higher S-adenosylmethionine (SAM)/S-adenosylhomocysteine (SAH) ratio and by elevated mRNA expression of serine hydroxymethyltransferase in both or either of the Se groups. Furthermore, increasing the Se supply resulted in higher plasma concentrations of triglycerides. Hepatic expression of glycolytic and lipogenic genes revealed consistent Se dependent up-regulation of glucokinase. The sterol regulatory element-binding transcription factor 1 (Srebf1) was also up-regulated by Se. Both effects were confirmed in primary hepatocytes. In contrast to the overall Se-dependent increase of methylation capacity, the up-regulation of Srebf1 expression was paralleled by reduced local methylation of a specific CpG site within the Srebf1 gene. Thus, we provided evidence that Se-dependent effects on lipogenesis involve epigenetic mechanisms. (C) 2017 The Authors. Published by Elsevier Inc.},
  language  = {en}
}
@article{HenzeHomannRohnetal.2016,
  author    = {Henze, Andrea and Homann, Thomas and Rohn, Isabelle and Aschner, Michael A. and Link, Christopher D. and Kleuser, Burkhard and Schweigert, Florian J. and Schwerdtle, Tanja and Bornhorst, Julia},
  title     = {Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin},
  series = {Scientific reports},
  volume    = {6},
  journal   = {Scientific reports},
  publisher = {Nature Publishing Group},
  address   = {London},
  issn      = {2045-2322},
  doi       = {10.1038/srep37346},
  pages     = {12},
  year      = {2016},
  abstract  = {The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.},
  language  = {en}
}