title: Does N-acetylcysteine modulate post-translational modifications of transthyretin in hemodialysis patients?
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.
authors.affiliation: 1 Institute of Nutritional Science, University of Potsdam , Nuthetal, Germany .
authors.forename: Andrea
authors.initials: A
authors.lastname: Henze
authors.forename: Jens
authors.initials: J
authors.lastname: Raila
authors.forename: Alexandra
authors.initials: A
authors.lastname: Scholze
authors.forename: Walter
authors.initials: W
authors.lastname: Zidek
authors.forename: Martin
authors.initials: M
authors.lastname: Tepel
authors.forename: Florian J
authors.initials: FJ
authors.lastname: Schweigert
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011228:Prealbumin / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D006435:Renal Dialysis
chemical_list: D011228:Prealbumin; D000111:Acetylcysteine