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An RNAi-based genetic screen for oxidative stress resistance reveals retinol saturase as a mediator of stress resistance
- Source :
-
Free Radical Biology & Medicine . Sep2007, Vol. 43 Issue 5, p781-788. 8p. - Publication Year :
- 2007
-
Abstract
- 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. [Copyright &y& Elsevier]
- Subjects :
- *VITAMIN A
*RNA
*NIACIN
*FREE radical reactions
Subjects
Details
- Language :
- English
- ISSN :
- 08915849
- Volume :
- 43
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Free Radical Biology & Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 25935653
- Full Text :
- https://doi.org/10.1016/j.freeradbiomed.2007.05.008