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

被引：6
作者：
Du, Zhen [1 ,2 ]
Chakrabarti, Sampurna [1 ]
Kulaberoglu, Yavuz [1 ,3 ]
Smith, Ewan St John [1 ]
Dobson, Christopher M. [2 ]
Itzhaki, Laura S. [1 ]
Kumita, Janet R. [1 ,2 ]
机构：
[1] Univ Cambridge, Dept Pharmacol, Tennis Court Rd, Cambridge CB2 1PD, England
[2] Univ Cambridge, Ctr Misfolding Dis, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England
[3] UCL Inst Hlth Ageing, Darwin Bldg,104 Gower St, London WC1E 6AD, England
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2020年 / 529卷 / 04期
基金：
英国惠康基金;
关键词：
Naked mole-rat; Unfolded protein response; ER stress; Protein homeostasis; Ageing; ENDOPLASMIC-RETICULUM STRESS; LIVING RODENT; MODEL; FIBROBLASTS; ACTIVATION; EXPRESSION; INDUCTION; LONGEVITY; INSIGHTS; SIGNALS;
D O I：
10.1016/j.bbrc.2020.06.118
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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. (C) 2020 The Author(s). Published by Elsevier Inc.
引用
收藏
页码：1151 / 1157
页数：7
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