@article{EspeRailaHenzeetal.2013,
  author    = {Espe, Katharina M. and Raila, Jens and Henze, Andrea and Blouin, Katja and Schneider, Andreas and Schmiedeke, Daniel and Krane, Vera and Pilz, Stefan and Schweigert, Florian J. and Hocher, Berthold and Wanner, Christoph and Drechsler, Christiane},
  title     = {Low plasma alpha-tocopherol concentrations and adverse clinical outcomes in diabetic hemodialysis patients},
  series = {Clinical journal of the American Society of Nephrology},
  volume    = {8},
  journal   = {Clinical journal of the American Society of Nephrology},
  number    = {3},
  publisher = {American Society of Nephrology},
  address   = {Washington},
  organization    = {German Diabet \& Dialysis Study Inv},
  issn      = {1555-9041},
  doi       = {10.2215/CJN.04880511},
  pages     = {452 -- 458},
  year      = {2013},
  abstract  = {Background and objectives Trials with the antioxidant vitamin E have failed to show benefit in the general population. Considering the different causes of death in ESRD, this study investigated the association between plasma concentrations of alpha-tocopherol and specific clinical outcomes in diabetic hemodialysis patients. Design, settings, participants, \& measurements In 1046 diabetic hemodialysis patients (participants of the German Diabetes and Dialysis Study), alpha-tocopherol was measured in plasma by reversed-phase HPLC. By Cox regression analyses, hazard ratios were determined for prespecified end points according to baseline plasma alpha-tocopherol levels: sudden death (n=134), myocardial infarction (n=172), stroke (n=89), combined cardiovascular events (n=398), fatal infection (n=107), and all-cause mortality (n=508). Results Patients had a mean age of 66 8 years, and mean plasma alpha-tocopherol level was 22.8+/-9.6 mu mol/L. Levels of alpha-tocopherol were highly correlated to triglycerides (r=0.63, P<0.001). Patients in the lowest alpha-tocopherol quartile had (in unadjusted analyses) a 79\% higher risk of stroke and a 31\% higher risk of all-cause mortality compared with patients in the highest quartile. The associations were attenuated after adjustment for confounders (hazard ratio(stroke)=1.56, 95\% confidence interval=0.75-3.25; hazard ratio(mortality)=1.22, 95\% confidence interval=0.89-1.69, respectively). There was no association between alpha-tocopherol and myocardial infarction, sudden death, or infectious death. Conclusions Plasma alpha-tocopherol concentrations were not independently associated with cardiovascular outcomes, infectious deaths, or all-cause mortality in diabetic hemodialysis patients. The lack of association can partly be explained by a confounding influence of malnutrition, which should be considered in the planning of trials to reduce cardiovascular risk in dialysis patients.},
  language  = {en}
}
@article{HenzeRailaScholzeetal.2013,
  author    = {Henze, Andrea and Raila, Jens and Scholze, Alexandra and Zidek, Walter and Tepel, Martin and Schweigert, Florian J.},
  title     = {Does N-Acetylcysteine modulate post-translational modifications of transthyretin in hemodialysis patients?},
  series = {Antioxidants \& redox signaling},
  volume    = {19},
  journal   = {Antioxidants \& redox signaling},
  number    = {11},
  publisher = {Liebert},
  address   = {New Rochelle},
  issn      = {1523-0864},
  doi       = {10.1089/ars.2012.5125},
  pages     = {1166 -- 1172},
  year      = {2013},
  abstract  = {It is assumed that effects of the thiol antioxidant N-acetylcysteine (NAC) are mediated by interaction with protein-associated cysteine residues, however, information on protein level in vivo are missing. Therefore, we analyzed NAC-induced modifications of the protein transthyretin (TTR) in plasma of hemodialysis patients in a randomized, placebo-controlled study. TTR was selected due to its low molecular weight and the free cysteine residue in the polypeptide chain, which is known to be extensively modified by formation of mixed disulfides. The intravenous application of NAC during a hemodialysis session resulted in a substantial increase of native TTR from median 15\% (range 8.8\%-30\%) to median 40\% (37-50) and reduction of S-cysteinylated TTR [51\% (44-60) vs. 6.6\% (2.4-10)]. Additionally the pronounced formation of a TTR-NAC adduct was detected. However, all these modifications seemed to be reversible. Additionally, in vitro incubation of plasma with NAC confirmed the in vivo results and indicated that changes in post-translational modification pattern of TTR were a function of NAC concentration. Based on these observations and the essential metabolic and biochemical role of protein-associated cysteine residues we hypothesize that the interaction of NAC with proteins may explain altered protein functions due to modification of cysteine residues. Antioxid. Redox Signal. 19, 1166-1172.},
  language  = {en}
}
@article{MuenznerTuviaDeutschmannetal.2013,
  author    = {M{\"u}nzner, Matthias and Tuvia, Neta and Deutschmann, Claudia and Witte, Nicole and Tolkachov, Alexander and Valai, Atijeh and Henze, Andrea and Sander, Leif E. and Raila, Jens and Schupp, Michael},
  title     = {Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by regulating cellular retinoid homeostasis and retinoic acid receptor alpha activity},
  series = {Molecular and cellular biology},
  volume    = {33},
  journal   = {Molecular and cellular biology},
  number    = {20},
  publisher = {American Society for Microbiology},
  address   = {Washington},
  issn      = {0270-7306},
  doi       = {10.1128/MCB.00221-13},
  pages     = {4068 -- 4082},
  year      = {2013},
  abstract  = {Retinoids are vitamin A (retinol) derivatives and complex regulators of adipogenesis by activating specific nuclear receptors, including the retinoic acid receptor (RAR) and retinoid X receptor (RXR). Circulating retinol-binding protein 4 (RBP4) and its membrane receptor STRA6 coordinate cellular retinol uptake. It is unknown whether retinol levels and the activity of RAR and RXR in adipocyte precursors are linked via RBP4/STRA6. Here, we show that STRA6 is expressed in precursor cells and, dictated by the apo-and holo-RBP4 isoforms, mediates bidirectional retinol transport that controls RAR alpha activity and subsequent adipocyte differentiation. Mobilization of retinoid stores in mice by inducing RBP4 secretion from the liver activated RAR alpha signaling in the precursor cell containing the stromal-vascular fraction of adipose tissue. Retinol-loaded holo-RBP4 blocked adipocyte differentiation of cultured precursors by activating RAR alpha. Remarkably, retinol-free apo-RBP4 triggered retinol efflux that reduced cellular retinoids, RAR alpha activity, and target gene expression and enhanced adipogenesis synergistically with ectopic STRA6. Thus, STRA6 in adipocyte precursor cells links nuclear RAR alpha activity to the circulating RBP4 isoforms, whose ratio in obese mice was shifted toward limiting the adipogenic potential of their precursors. This novel cross talk identifies a retinoldependent metabolic function of RBP4 that may have important implications for the treatment of obesity.},
  language  = {en}
}
@inproceedings{HenzeRailaScholzeetal.2013,
  author    = {Henze, Andrea and Raila, Jens and Scholze, Alexandra and Schweigert, Florian J. and Tepel, Martin},
  title     = {Administration of N-Acetylcyteine causes beneficial posttranslationalmodifications of transthyretin in hemodialysis patients},
  series = {Nephrology, dialysis, transplantation},
  volume    = {28},
  booktitle = {Nephrology, dialysis, transplantation},
  number    = {2},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0931-0509},
  pages     = {164 -- 164},
  year      = {2013},
  language  = {en}
}