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 Citations (Scopus)

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
StatePublished - Nov 21 2016

Fingerprint

Prealbumin
Caenorhabditis elegans
Post Translational Protein Processing
Pharmaceutical Preparations
Vitamin K 3
Penicillamine
Life Cycle Stages
Mass Spectrometry
Lasers
Proteins

ASJC Scopus subject areas

  • General

Cite this

Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin. / Henze, Andrea; Homann, Thomas; Rohn, Isabelle; Aschner, Michael; Link, Christopher D.; Kleuser, Burkhard; Schweigert, Florian J.; Schwerdtle, Tanja; Bornhorst, Julia.

In: Scientific Reports, Vol. 6, 37346, 21.11.2016.

Research output: Contribution to journalArticle

Henze, A, Homann, T, Rohn, I, Aschner, M, Link, CD, Kleuser, B, Schweigert, FJ, Schwerdtle, T & Bornhorst, J 2016, 'Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin', Scientific Reports, vol. 6, 37346. https://doi.org/10.1038/srep37346
Henze, Andrea ; Homann, Thomas ; Rohn, Isabelle ; Aschner, Michael ; Link, Christopher D. ; Kleuser, Burkhard ; Schweigert, Florian J. ; Schwerdtle, Tanja ; Bornhorst, Julia. / Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin. In: Scientific Reports. 2016 ; Vol. 6.
@article{59a289421cf7450a8f1f39a7b2f8458a,
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.",
author = "Andrea Henze and Thomas Homann and Isabelle Rohn and Michael Aschner and Link, {Christopher D.} and Burkhard Kleuser and Schweigert, {Florian J.} and Tanja Schwerdtle and Julia Bornhorst",
year = "2016",
month = "11",
day = "21",
doi = "10.1038/srep37346",
language = "English (US)",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin

AU - Henze, Andrea

AU - Homann, Thomas

AU - Rohn, Isabelle

AU - Aschner, Michael

AU - Link, Christopher D.

AU - Kleuser, Burkhard

AU - Schweigert, Florian J.

AU - Schwerdtle, Tanja

AU - Bornhorst, Julia

PY - 2016/11/21

Y1 - 2016/11/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84996557519&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84996557519&partnerID=8YFLogxK

U2 - 10.1038/srep37346

DO - 10.1038/srep37346

M3 - Article

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 37346

ER -