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An RNAi-based genetic screen for oxidative stress resistance reveals retinol saturase as a mediator of stress resistance

Rie Nagaoka-Yasuda, Naoki Matsuo, Brian Perkins Orcid Logo, Klara Limbaeck-Stokin, Mark Mayford

Free Radical Biology and Medicine, Volume: 43, Issue: 5, Pages: 781 - 788

Swansea University Author: Brian Perkins Orcid Logo

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DOI (Published version): 10.1016/j.freeradbiomed.2007.05.008

Abstract

Oxidative stress has been implicated in the pathogenesis of numerous late-onset diseases as well as organismal longevity. Nevertheless, the genetic components that affect cellular sensitivity to oxidative stress have not been explored extensively at the genome-wide level in mammals. Here we report a...

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Published in: Free Radical Biology and Medicine
Published: 2007
Online Access: http://www.sciencedirect.com/science/article/pii/S0891584907003243
URI: https://cronfa.swan.ac.uk/Record/cronfa20486
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first_indexed 2015-03-20T03:04:00Z
last_indexed 2018-02-09T04:57:04Z
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spelling 2015-03-19T11:44:14.3311663 v2 20486 2015-03-19 An RNAi-based genetic screen for oxidative stress resistance reveals retinol saturase as a mediator of stress resistance ba13cfe67917998691f44342815a243e 0000-0001-9281-5909 Brian Perkins Brian Perkins true false 2015-03-19 PMSC Oxidative stress has been implicated in the pathogenesis of numerous late-onset diseases as well as organismal longevity. Nevertheless, the genetic components that affect cellular sensitivity to oxidative stress have not been explored extensively at the genome-wide level in mammals. Here we report an RNA interference (RNAi) screen for genes that increase resistance to an organic oxidant, tert-butylhydroperoxide (tert-BHP), in cultured fibroblasts. The loss-of-function screen allowed us to identify several short hairpin RNAs (shRNAs) that elevated the cellular resistance to tert-BHP. One of these shRNAs strongly protected cells from tert-BHP and H2O2 by specifically reducing the expression of retinol saturase, an enzyme that converts all-trans-retinol (vitamin A) to all-trans-13,14-dihydroretinol. The protective effect was well correlated with the reduction in mRNA level and was observed in both primary fibroblasts and NIH3T3 cells. The results suggest a novel role for retinol saturase in regulating sensitivity to oxidative stress and demonstrate the usefulness of large-scale RNAi screening for elucidating new molecular pathways involved in stress resistance. Journal Article Free Radical Biology and Medicine 43 5 781 788 Stress resistance; RNA interference; Genetic screen; Oxidative stress; tert-Butylhydroperoxide; Free radicals 16 5 2007 2007-05-16 10.1016/j.freeradbiomed.2007.05.008 http://www.sciencedirect.com/science/article/pii/S0891584907003243 COLLEGE NANME Medicine COLLEGE CODE PMSC Swansea University 2015-03-19T11:44:14.3311663 2015-03-19T11:35:45.5658359 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Rie Nagaoka-Yasuda 1 Naoki Matsuo 2 Brian Perkins 0000-0001-9281-5909 3 Klara Limbaeck-Stokin 4 Mark Mayford 5
title An RNAi-based genetic screen for oxidative stress resistance reveals retinol saturase as a mediator of stress resistance
spellingShingle An RNAi-based genetic screen for oxidative stress resistance reveals retinol saturase as a mediator of stress resistance
Brian Perkins
title_short An RNAi-based genetic screen for oxidative stress resistance reveals retinol saturase as a mediator of stress resistance
title_full An RNAi-based genetic screen for oxidative stress resistance reveals retinol saturase as a mediator of stress resistance
title_fullStr An RNAi-based genetic screen for oxidative stress resistance reveals retinol saturase as a mediator of stress resistance
title_full_unstemmed An RNAi-based genetic screen for oxidative stress resistance reveals retinol saturase as a mediator of stress resistance
title_sort An RNAi-based genetic screen for oxidative stress resistance reveals retinol saturase as a mediator of stress resistance
author_id_str_mv ba13cfe67917998691f44342815a243e
author_id_fullname_str_mv ba13cfe67917998691f44342815a243e_***_Brian Perkins
author Brian Perkins
author2 Rie Nagaoka-Yasuda
Naoki Matsuo
Brian Perkins
Klara Limbaeck-Stokin
Mark Mayford
format Journal article
container_title Free Radical Biology and Medicine
container_volume 43
container_issue 5
container_start_page 781
publishDate 2007
institution Swansea University
doi_str_mv 10.1016/j.freeradbiomed.2007.05.008
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
url http://www.sciencedirect.com/science/article/pii/S0891584907003243
document_store_str 0
active_str 0
description Oxidative stress has been implicated in the pathogenesis of numerous late-onset diseases as well as organismal longevity. Nevertheless, the genetic components that affect cellular sensitivity to oxidative stress have not been explored extensively at the genome-wide level in mammals. Here we report an RNA interference (RNAi) screen for genes that increase resistance to an organic oxidant, tert-butylhydroperoxide (tert-BHP), in cultured fibroblasts. The loss-of-function screen allowed us to identify several short hairpin RNAs (shRNAs) that elevated the cellular resistance to tert-BHP. One of these shRNAs strongly protected cells from tert-BHP and H2O2 by specifically reducing the expression of retinol saturase, an enzyme that converts all-trans-retinol (vitamin A) to all-trans-13,14-dihydroretinol. The protective effect was well correlated with the reduction in mRNA level and was observed in both primary fibroblasts and NIH3T3 cells. The results suggest a novel role for retinol saturase in regulating sensitivity to oxidative stress and demonstrate the usefulness of large-scale RNAi screening for elucidating new molecular pathways involved in stress resistance.
published_date 2007-05-16T03:24:14Z
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score 11.037122

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