Genome-wide transcriptional responses to a lipid hydroperoxide: Adaptation occurs without induction of oxidant defenses

被引:34
作者
Alic, N
Felder, T
Temple, MD
Gloeckner, C
Higgins, VJ
Briza, P
Dawes, IW [1 ]
机构
[1] Univ New S Wales, BABS, Ramaciotti Ctr Gene Funct Anal, Sydney, NSW 2052, Australia
[2] Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia
[3] Salzburg Univ, Dept Genet & Gen Biol, A-5020 Salzburg, Austria
基金
澳大利亚研究理事会; 奥地利科学基金会;
关键词
oxidative stress; lipid peroxidation; adaptive response; transcription; pleiotropic drug resistance; free radicals;
D O I
10.1016/j.freeradbiomed.2004.04.014
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
Free radicals can initiate the oxidation of polyunsaturated fatty acids in cells through the process of lipid peroxidation. The genome-wide transcriptional changes in Saccharomyces cerevisiae after treatment with the toxic lipid peroxidation product linoleic acid hydroperoxide (LoaOOH) were identified. High-dose treatment led to a switch in transcription from biosynthetic to protective functions. This response encompassed a set of genes stimulated predominantly by LoaOOH, and not by other oxidants or heat shock, which contained components of the pleiotropic drug resistance system. The dose dependence of the transcriptional response revealed that large and widespread changes occur only in response to higher doses. Pretreatment of cells with sublethal doses of LoaOOH induces resistance to an otherwise lethal dose through the process of adaptation. Adaptive doses elicited a more subtle transcriptional response affecting metabolic functions, including an increase in the capacity for detoxification and downregulation of the rate of protein synthesis. Surprisingly, the cellular response to adaptive doses did not include induction of oxidative-stress defense enzymes nor of transcripts involved in general cellular defense systems. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:23 / 35
页数:13
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