TY - JOUR A1 - Frey, Simone K. A1 - Henze, Andrea A1 - Nagl, Britta A1 - Raila, Jens A1 - Scholze, Alexandra A1 - Tepel, Martin A1 - Schweigert, Florian J. A1 - Zidek, Walter T1 - Effect of renal replacement therapy on retinol-binding protein 4 isoforms N2 - 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. Y1 - 2009 UR - http://www.sciencedirect.com/science/journal/00098981 U6 - https://doi.org/10.1016/j.cca.2008.11.008 SN - 0009-8981 ER - TY - JOUR A1 - Henze, Andrea A1 - Raila, Jens A1 - Scholze, Alexandra A1 - Zidek, Walter A1 - Tepel, Martin A1 - Schweigert, Florian J. T1 - Does N-Acetylcysteine modulate post-translational modifications of transthyretin in hemodialysis patients? JF - Antioxidants & redox signaling N2 - 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. Y1 - 2013 U6 - https://doi.org/10.1089/ars.2012.5125 SN - 1523-0864 VL - 19 IS - 11 SP - 1166 EP - 1172 PB - Liebert CY - New Rochelle ER - TY - JOUR A1 - Henze, Andrea A1 - Frey, Simone K. A1 - Raila, Jens A1 - Scholze, Alexandra A1 - Spranger, Joachim A1 - Weickert, Martin O. A1 - Tepel, Martin A1 - Zidek, Walter A1 - Schweigert, Florian J. T1 - Alterations of retinol-binding protein 4 species in patients with different stages of chronic kidney disease and their relation to lipid parameters N2 - 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. Y1 - 2010 UR - http://www.sciencedirect.com/science/journal/0006291X U6 - https://doi.org/10.1016/j.bbrc.2010.01.082 SN - 0006-291X ER - TY - CHAP A1 - Henze, Andrea A1 - Raila, Jens A1 - Scholze, Alexandra A1 - Schweigert, Florian J. A1 - Tepel, Martin T1 - Administration of N-Acetylcyteine causes beneficial posttranslationalmodifications of transthyretin in hemodialysis patients T2 - Nephrology, dialysis, transplantation Y1 - 2013 SN - 0931-0509 VL - 28 IS - 2 SP - 164 EP - 164 PB - Oxford Univ. Press CY - Oxford ER -