Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin

Andrea Henze, Thomas Homann, Isabelle Rohn, Michael Aschner, Christopher D. Link, Burkhard Kleuser, Florian J. Schweigert, Tanja Schwerdtle, Julia Bornhorst

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Article number37346
JournalScientific reports
Volume6
DOIs
Publication statusPublished - Nov 21 2016

    Fingerprint

ASJC Scopus subject areas

  • General

Cite this