Journal article 894 views
An RNAi-based genetic screen for oxidative stress resistance reveals retinol saturase as a mediator of stress resistance
,
Klara Limbaeck-Stokin,
Mark Mayford
Free Radical Biology and Medicine, Volume: 43, Issue: 5, Pages: 781 - 788
Swansea University Author:
Brian Perkins
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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...
| Published in: | Free Radical Biology and Medicine |
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| Published: |
2007
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| Online Access: |
http://www.sciencedirect.com/science/article/pii/S0891584907003243 |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa20486 |
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| 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 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. |
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| Keywords: |
Stress resistance; RNA interference; Genetic screen; Oxidative stress; tert-Butylhydroperoxide; Free radicals |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Issue: |
5 |
| Start Page: |
781 |
| End Page: |
788 |