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Erschienen in: European Journal of Nutrition 2/2020

31.01.2019 | Original Contribution

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

verfasst von: Mehtap Civelek, Sandra Flory, Hedda Meloh, Elena Fitzenberger, Uwe Wenzel

Erschienen in: European Journal of Nutrition | Ausgabe 2/2020

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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.
Literatur
3.
Zurück zum Zitat Chevion M, Berenshtein E, Stadtman ER (2000) Human studies related to protein oxidation: protein carbonyl content as a marker of damage. Free Radic Res 33:S99–S108PubMed Chevion M, Berenshtein E, Stadtman ER (2000) Human studies related to protein oxidation: protein carbonyl content as a marker of damage. Free Radic Res 33:S99–S108PubMed
4.
Zurück zum Zitat Beal MF (2002) Oxidatively modified proteins in aging and disease. Free Radic Biol Med 32(9):797–803CrossRef Beal MF (2002) Oxidatively modified proteins in aging and disease. Free Radic Biol Med 32(9):797–803CrossRef
5.
Zurück zum Zitat Puddu A, Viviani GL (2011) Advanced glycation endproducts and diabetes. Beyond vascular complications. Endocr Metab Immune Disord Drug Targets 11(2):132–140CrossRef Puddu A, Viviani GL (2011) Advanced glycation endproducts and diabetes. Beyond vascular complications. Endocr Metab Immune Disord Drug Targets 11(2):132–140CrossRef
7.
Zurück zum Zitat Mooradian AD, Thurman JE (1999) Glucotoxicity: potential mechanisms. Clin Geriatr Med 15(2):255CrossRef Mooradian AD, Thurman JE (1999) Glucotoxicity: potential mechanisms. Clin Geriatr Med 15(2):255CrossRef
9.
17.
Zurück zum Zitat Timmons L, Court DL, Fire A (2001) Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263(1–2):103–112CrossRef Timmons L, Court DL, Fire A (2001) Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263(1–2):103–112CrossRef
30.
Zurück zum Zitat Olzmann JA, Li L, Chin LS (2008) Aggresome formation and neurodegenerative diseases: therapeutic implications. Curr Med Chem 15(1):47–60CrossRef Olzmann JA, Li L, Chin LS (2008) Aggresome formation and neurodegenerative diseases: therapeutic implications. Curr Med Chem 15(1):47–60CrossRef
Metadaten
Titel
The polyphenol quercetin protects from glucotoxicity depending on the aggresome in Caenorhabditis elegans
verfasst von
Mehtap Civelek
Sandra Flory
Hedda Meloh
Elena Fitzenberger
Uwe Wenzel
Publikationsdatum
31.01.2019
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nutrition / Ausgabe 2/2020
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-019-01917-6

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