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Probing the unfolded protein response in long-lived naked mole-rats.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Du, Zhen 
Chakrabarti, Sampurna 
Kulaberoglu, Yavuz 
Smith, Ewan St John 
Dobson, Christopher M 

Abstract

The long-living naked mole-rat (NMR) shows negligible senescence and resistance to age-associated diseases. Recent evidence, based on protein-level assays, suggests that enhanced protein homeostasis machinery contributes to NMR stress-resistance and longevity. Here, we develop NMR-specific, transcriptional assays for measuring the unfolded protein response (UPR), a component of ER proteostasis. By varying doses and response times of pharmacological ER stressors applied to NMR kidney fibroblasts, we probe the NMR UPR in detail, demonstrating that NMR fibroblasts have a higher UPR activation threshold compared to mouse fibroblasts under mild ER-stress induction; whereas temporal analysis reveals that severe ER-stress induction results in no comparative differences. Probing NMR UPR activation with our robust assays may lead to insights into the proteostasis and ageing relationship.

Description

Keywords

Ageing, ER stress, Naked mole-rat, Protein homeostasis, Unfolded protein response, Animals, Apoptosis, Cells, Cultured, Endoplasmic Reticulum, Endoplasmic Reticulum Stress, Endoplasmic Reticulum-Associated Degradation, Female, Fibroblasts, Gene Expression Regulation, Kidney, Longevity, Male, Mice, Mole Rats, Protein Folding, Protein Serine-Threonine Kinases, RNA Splicing, Unfolded Protein Response, X-Box Binding Protein 1

Journal Title

Biochem Biophys Res Commun

Conference Name

Journal ISSN

0006-291X
1090-2104

Volume Title

529

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (094425/Z/10/Z)
Cancer Research UK (via Newcastle University) (BH151657 / NS/A000039/1)
Herchel Smith PhD Research Scholarship Rosetrees Trust Gates Cambridge Trust scholarship