title: Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin.
abstract: The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.
authors.affiliation: Department of Physiology and Pathophysiology, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Henze
authors.affiliation: Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.|Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Homann
authors.affiliation: Department of Physiology and Pathophysiology, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.|Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.|Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Rohn
authors.affiliation: Department of Molecular Pharmacology, Neuroscience, and Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 10461 Bronx, NY, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Aschner
authors.affiliation: Institute for Behavioral Genetics, University of Colorado at Boulder, 1480 30th St., 80303 Boulder, CO, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Link
authors.affiliation: Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Kleuser
authors.affiliation: Department of Physiology and Pathophysiology, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Florian J
authors.initials: FJ
authors.lastname: Schweigert
authors.affiliation: Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Schwerdtle
authors.affiliation: Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bornhorst
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D015870:Gene Expression; D006801:Humans; D008958:Models, Molecular; D011228:Prealbumin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D019076:Transgenes
chemical_list: D011228:Prealbumin