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

  • 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, forThe 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.show moreshow less

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Metadaten
Author:Andrea HenzeORCiDGND, Thomas Homann, Isabelle Rohn, Michael Aschner, Christopher D. Link, Burkhard KleuserORCiDGND, Florian J. SchweigertORCiDGND, Tanja Schwerdtle, Julia Bornhorst
URN:urn:nbn:de:kobv:517-opus4-103674
Series (Serial Number):Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (312)
Document Type:Postprint
Language:English
Date of first Publication:2016/11/21
Year of Completion:2016
Publishing Institution:Universität Potsdam
Release Date:2017/02/22
Tag:binding; c. elegans; cells; disease; force-field; life-span; menadione; n-acetyl-cysteine; protein; s-glutathionylation
Pagenumber:12
Source:Scientific reports 6:37346 (2016). - DOI: 10.1038/srep37346
Funder:Universität Potsdam, Publikationsfonds
Grant Number:PA 2016_41
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 50 Naturwissenschaften / 500 Naturwissenschaften und Mathematik
5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Peer Review:Referiert
Publication Way:Open Access
Licence (German):License LogoCreative Commons - Namensnennung, 4.0 International
Notes extern:Bibliographieeintrag der Originalveröffentlichung/Quelle