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 - TY - CHAP A1 - Hocher, Berthold A1 - Armbruster, Franz Paul A1 - Scholze, Alexandra A1 - Marckmann, Peter A1 - Reichetzeder, Christoph A1 - Roth, Heinz Jürgen A1 - Tepel, Martin T1 - Non-oxidized, biological active parathyroid hormone determines motality in hemodialsysis patients T2 - Nephrology, dialysis, transplantation Y1 - 2013 SN - 0931-0509 VL - 28 SP - 33 EP - 33 PB - Oxford Univ. Press CY - Oxford 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 - Tepel, Martin A1 - Armbruster, Franz Paul A1 - Groen, Hans Juergen A1 - Scholze, Alexandra A1 - Reichetzeder, Christoph A1 - Roth, Heinz Jürgen A1 - Hocher, Berthold T1 - Nonoxidized, biologically active parathyroid hormone determines mortality in hemodialysis patients JF - The journal of clinical endocrinology & metabolism N2 - Background: It was shown that nonoxidized PTH (n-oxPTH) is bioactive, whereas the oxidation of PTH results in a loss of biological activity. Methods: In this study we analyzed the association of n-oxPTH on mortality in hemodialysis patients using a recently developed assay system. Results: Hemodialysis patients (224 men, 116 women) had a median age of 66 years. One hundred seventy patients (50%) died during the follow-up period of 5 years. Median n-oxPTH levels were higher in survivors (7.2 ng/L) compared with deceased patients (5.0 ng/L; P = .002). Survival analysis showed an increased survival in the highest n-oxPTH tertile compared with the lowest n-oxPTH tertile (chi(2), 14.3; P = 0008). Median survival was 1702 days in the highest n-oxPTH tertile, whereas it was only 453 days in the lowest n-oxPTH tertile. Multivariable-adjusted Cox regression showed that higher age increased odds for death, whereas higher n-oxPTH reduced the odds for death. Another model analyzing a subgroup of patients with intact PTH (iPTH) concentrations at baseline above the upper normal range of the iPTH assay (70 ng/L) revealed that mortality in this subgroup was associated with oxidized PTH but not with n-oxPTH levels. Conclusions: The predictive power of n-oxPTH and iPTH on the mortality of hemodialysis patients differs substantially. Measurements of n-oxPTH may reflect the hormone status more precisely. The iPTH-associated mortality is most likely describing oxidative stress-related mortality. Y1 - 2013 U6 - https://doi.org/10.1210/jc.2013-2139 SN - 0021-972X SN - 1945-7197 VL - 98 IS - 12 SP - 4744 EP - 4751 PB - Endocrine Society CY - Chevy Chase ER -