Genome-wide transcriptional responses to a lipid hydroperoxide: adaptation occurs without induction of oxidant defenses.
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.
Alic
Nazif
N
Ramaciotti Centre for Gene Function Analysis and School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, 2052 NSW, Australia.
Felder
Thomas
T
Temple
Mark D
MD
Gloeckner
Christian
C
Higgins
Vincent J
VJ
Briza
Peter
P
Dawes
Ian W
IW
D005656:Fungal Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D016681:Genome, Fungal; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*
D005656:Fungal Proteins; D008054:Lipid Peroxides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species