@article{PrueferSchuchardtToelleetal.2014,
  author    = {Pruefer, Jasmin and Schuchardt, Mirjam and Toelle, Markus and Pruefer, Nicole and Hoehne, Matthias and Zidek, Walter and van der Giet, Markus},
  title     = {Harmful effects of the azathioprine metabolite 6-mercaptopurine in vascular cells: Induction of mineralization},
  series = {PLoS one},
  volume    = {9},
  journal   = {PLoS one},
  number    = {7},
  publisher = {PLoS},
  address   = {San Fransisco},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0101709},
  pages     = {8},
  year      = {2014},
  abstract  = {Vascular mineralization contributes to the high cardiovascular morbidity and mortality in patients who suffer from chronic kidney disease and in individuals who have undergone solid organ transplantation. The immunosuppressive regimen used to treat these patients appears to have an impact on vascular alterations. The effect of 6-mercaptopurine (6-MP) on vascular calcification has not yet been determined. This study investigates the effect of 6-MP on vascular mineralization by the induction of trans-differentiation of rat vascular smooth muscle cells in vitro. 6-MP not only induces the expression of osteochondrocyte-like transcription factors and proteins but also activates alkaline phosphatase enzyme activity and produces calcium deposition in in vitro and ex vivo models. These processes are dependent on 6-MP-induced production of reactive oxygen species, intracellular activation of mitogen-activated kinases and phosphorylation of the transcription factor Cbfa1. Furthermore, the metabolic products of 6-MP, 6-thioguanine nucleotides and 6-methyl-thio-inosine monophosphate have major impacts on cellular calcification. These data provide evidence for a possible harmful effect of the immunosuppressive drug 6-MP in vascular diseases, such as arteriosclerosis.},
  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{HenzeFreyRailaetal.2010,
  author    = {Henze, Andrea and Frey, Simone K. and Raila, Jens and Scholze, Alexandra and Spranger, Joachim and Weickert, Martin O. and Tepel, Martin and Zidek, Walter and Schweigert, Florian J.},
  title     = {Alterations of retinol-binding protein 4 species in patients with different stages of chronic kidney disease and their relation to lipid parameters},
  issn      = {0006-291X},
  doi       = {10.1016/j.bbrc.2010.01.082},
  year      = {2010},
  abstract  = {Retinol-binding protein 4 (RBP4) is elevated in patients with chronic kidney disease (CKD) and has been discussed as marker of kidney function. In addition to an elevated concentration, the existence of truncated RBP4 species, RBP4-L (truncated at last C-terminal leucine) and RBP4-LL (truncated at both C-terminal leucines), has been reported in serum of hemodialysis patients. Since little is known about the occurrence of RBP4 species during the progression of CKD it was the aim of this study to analyse this possible association. The presence of RBP4, RBP4-L, RBP4- LL and transthyretin (TTR) was assessed in serum of 45 healthy controls and 52 patients with stage 2-5 of CKD using ELISA and RBP4 immunoprecipitation with subsequent MALDI-TOF-MS analysis. A reduction of glomerular filtration rate was accompanied by a gradual elevation of RBP4 serum levels and relative amounts of RBP4-LL. Correlation analysis revealed a strong association of the RBP4-TTR ratio with parameters of lipid metabolism and with diabetes-related factors. In conclusion, RBP4 serum concentration and the appearance of RBP4-LL seem to be influenced by kidney function. Furthermore, the RBP4-TTR ratio may provide diagnostic potential with regard to metabolic complications in CKD patients.},
  language  = {en}
}
@article{FreyHenzeNagletal.2009,
  author    = {Frey, Simone K. and Henze, Andrea and Nagl, Britta and Raila, Jens and Scholze, Alexandra and Tepel, Martin and Schweigert, Florian J. and Zidek, Walter},
  title     = {Effect of renal replacement therapy on retinol-binding protein 4 isoforms},
  issn      = {0009-8981},
  doi       = {10.1016/j.cca.2008.11.008},
  year      = {2009},
  abstract  = {Background: Retinol-binding protein 4 (RBP4) levels are elevated in the serum of patients with kidney dysfunction. We recently showed that RBP4 isoforms including apo-RBP4 (RBP4 not bound to retinol) and RBP4 truncated at the C-terminus (RBP4-L, RBP4-LL) are increased in the serum of patients with kidney diseases but not in serum of patients with various liver diseases. The aim of this study was to investigate the effect of renal replacement therapy on RBP4 isoforms. Methods: We investigated serum levels of RBP4, apo-RBP4, holo-RBP4, RBP4-L, RBP4-LL, retinol and transthyretin (TTR) in 18 hemodialysis (HD) patients, 30 patients after renal transplantation (RTx) and in 35 healthy controls. RBP4 and TTR levels were measured by enzyme-linked immunosorbent assay, apo- and holo-RBP4 by native electrophoresis, retinol by high performance liquid chromatography and RBP4-L and RBP4-LL were analyzed by mass spectrometry. Results: HD and RTx patients had elevated RBP4, apo-RBP4 and RBP4-LL levels compared to controls. RTx patients had elevated amounts of RBP4-L compared to controls and elevated RBP4 and apo-RBP4 levels compared to HD patients. Conclusion: The results demonstrate a strong correlation between kidney function and RBP4 isoforms and provide data for investigating the relation of RBP4 and insulin resistance in these patients.},
  language  = {en}
}
@article{GiebingToelleJuergensenetal.2005,
  author    = {Giebing, G{\"u}nter and T{\"o}lle, Markus and J{\"u}rgensen, Jana and Eichhorst, Jenny and Furkert, Jens and Beyermann, Michael and Neusch{\"a}fer-Rube, Frank and Rosenthal, Walter and Zidek, Walter and van der Giet, Markus and Oksche, Alexander},
  title     = {Arrestin-independent internalization and recycling of the urotensin receptor contribute to long-lasting urotensin II - Mediated vasoconstriction},
  issn      = {0009-7330},
  year      = {2005},
  abstract  = {Urotensin II (UII), which acts on the G protein-coupled urotensin ( UT) receptor, elicits long-lasting vasoconstriction. The role of UT receptor internalization and intracellular trafficking in vasoconstriction has yet not been analyzed. Therefore, UII-mediated contractile responses of aortic ring preparations in wire myography and rat UT (rUT) receptor internalization and intracellular trafficking in binding and imaging analyses were compared. UII elicited a concentration-dependent vasoconstriction of rat aorta (-log EC50, mol/L:9.0 +/- 0.1). A second application of UII after 30 minutes elicited a reduced contraction (36 +/- 4\% of the initial response), but when applied after 60 minutes elicited a full contraction. In internalization experiments with radioactive labeled VII (I-125-UII), approximate to 70\% of rUT receptors expressed on the cell surface of human embryonic kidney 293 cells were sequestered within 30 minutes (half life [t(h)]: 5.6 +/- 0.2 minutes), but recycled quantitatively within 60 minutes (t(h) 31.9 +/- 2.6 minutes). UII- bound rUT receptors were sorted to early and recycling endosomes, as evidenced by colocalization of rUT receptors with the early endosomal antigen and the transferrin receptor. Real-time imaging with a newly developed fluorescent UII (Cy3- UII) revealed that rUT receptors recruited arrestin3 green fluorescent protein to the plasma membrane. Arrestin3 was not required for the endocytosis of the rUT receptor, however, as internalization of Cy3-UII was not altered in mouse embryonic fibroblasts lacking endogenous arrestin2/arrestin3 expression. The data demonstrate that the rUT receptor internalizes arrestin independently and recycles quantitatively. The continuous externalization of rUT receptors provides the basis for repetitive and lasting UII-mediated vasoconstriction},
  language  = {en}
}