Article

 

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

https://scholar.colorado.edu/concern/articles/n870zr301
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.
Creator
Date Issued
  • 2016-11-21
Academic Affiliation
Journal Title
Journal Volume
  • 6
File Extent
  • 37346-37346
最新修改
  • 2019-12-05
Identifier
  • PubMed ID: 27869126
Resource Type
权利声明
DOI
ISSN
  • 2045-2322
Language

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