Lipid hydroperoxides activate the mitogen-activated protein kinase Mpk1p in Saccharomyces cerevisiae.
Saccharomyces cerevisiae is capable of responding to oxidants, including lipid peroxidation products. We investigate here the role of the mitogen-activated protein kinase Mpk1p in protection against linoleic acid hydroperoxide (LoaOOH), a product of radical attack on an unsaturated lipid. MPK1 was found to be required for resistance to LoaOOH. Furthermore, Mpk1p was rapidly and transiently phosphorylated in response to LoaOOH. This phosphorylation was dose-dependent and stimulated by sublethal concentrations as low as 1 mum in the external medium. Such low doses have been shown to result in resistance to subsequent challenge with a higher dose through the process of adaptation. However MPK1 was not essential for this adaptive response. MPK1 was also not involved in cell cycle modulation and acted independently of the cell cycle-regulating Oca1p. Transcriptional profiling of the mpk1Delta cells during LoaOOH stress indicated that Mpk1p may be important in effecting changes to the cell surface and metabolism during LoaOOH exposure. Furthermore, it revealed that Mpk1p is required for the regulation of 97 LoaOOH-responsive transcripts. Evidence is presented that the activation of Mpk1p may be caused by the activation of protein kinase C by LoaOOH.
Alic
Nazif
N
Ramaciotti Centre for Gene Function Analysis, School of Biotechnology and Biomolecular Sciences, University of New South Wales, 2052 New South Wales, Australia.
Higgins
Vincent J
VJ
Pichova
Alena
A
Breitenbach
Michael
M
Dawes
Ian W
IW
D000222:Adaptation, Physiological; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D008041:Linoleic Acids / Q000494:pharmacology; D008054:Lipid Peroxides / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases; D018384:Oxidative Stress / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology
D008041:Linoleic Acids; D008054:Lipid Peroxides; D029701:Saccharomyces cerevisiae Proteins; C008285:linoleic acid hydroperoxide; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae