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The polyphenol quercetin protects from glucotoxicity depending on the aggresome in Caenorhabditis elegans

  • Mehtap Civelek
  • Sandra Flory
  • Hedda Meloh
  • Elena Fitzenberger
  • Uwe WenzelEmail author
Original Contribution
  • 38 Downloads

Abstract

Purpose

Impaired proteostasis, i.e., protein homeostasis, is considered as a consequence of high-glucose exposure and is associated with reduced survival. The previous studies demonstrated that the polyphenol quercetin can protect from glucotoxicity. The aim of the present study was to unravel the contribution of the aggresome, sequestering potentially cytotoxic aggregates and also acting as a staging center for eventual autophagic clearance from the cell.

Methods

Knockdown of the aggresome-relevant genes dnc-1 and ubql-1 was achieved in stress-sensitive mev-1 mutants of the nematode Caenorhabditis elegans by RNA interference (RNAi). Survival assay was conducted under heat stress at 37 °C, protein aggregation using ProteoStat® and chymotrypsin-like proteasomal activity according to the cleavage of a fluorogenic peptide substrate.

Results

Survival was reduced by knockdown of ubql-1 and even more by knockdown of dnc-1 which both were not further reduced by addition of glucose. The rescue of survival due to quercetin in glucose-exposed nematodes was completely prevented under RNAi versus ubql-1 or dnc-1. Both knockdowns caused an increase of aggregated protein and prevented the reduction of aggregated protein caused by quercetin in glucose-exposed animals. Finally, the knockdown of ubql-1 and dnc-1 blocked the increase of proteasomal activity achieved by quercetin in glucose-treated nematodes.

Conclusions

The study provides evidence that quercetin protects C. elegans from glucotoxicity through the activation of the aggresome, thereby, quercetin prevents the aggregation and functional loss of proteins, which is typically caused by enhanced glucose concentrations.

Keywords

Aggresome Proteasome Caenorhabditis elegans Glucotoxicity Quercetin Survival 

Abbreviations

C. elegans

Caenorhabditis elegans

DNC-1

Dynactin complex component

dsRNA

Double-stranded RNA

E. coli

Escherichia coli

IPTG

Isopropyl-β-d-thiogalactopyranoside

RNAi

RNA interference

ROS

Reactive oxygen species

SQST-1

Sequestosome-related 1

UBQL-1

Ubiquilin 1

Notes

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Mehtap Civelek
    • 1
  • Sandra Flory
    • 1
  • Hedda Meloh
    • 1
  • Elena Fitzenberger
    • 1
  • Uwe Wenzel
    • 1
    Email author
  1. 1.Interdisciplinary Research CenterJustus-Liebig-University of GiessenGiessenGermany

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