Title: Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin.
Authors: Henze, Andrea; Homann, Thomas; Rohn, Isabelle; Aschner, Michael; Link, Christopher D; Kleuser, Burkhard; Schweigert, Florian J; Schwerdtle, Tanja; Bornhorst, Julia
Published In Sci Rep, (2016 11 21)
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.
PubMed ID: 27869126
MeSH Terms: Animals; Caenorhabditis elegans; Gene Expression; Humans; Models, Molecular; Prealbumin/chemistry; Prealbumin/genetics; Prealbumin/metabolism*; Protein Processing, Post-Translational*; Transgenes