The yeast glutaredoxins are active as glutathione peroxidases

被引:109
作者
Collinson, EJ
Wheeler, GL
Garrido, EO
Avery, AM
Avery, SV
Grant, CM
机构
[1] Univ Manchester, Inst Sci & Technol, Dept Biomol Sci, Manchester M60 1QD, Lancs, England
[2] Univ Nottingham, Sch Life & Environm Sci, Nottingham NG7 2RD, England
关键词
D O I
10.1074/jbc.M111686200
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
The yeast Saccharomyces cerevisiae contains two glutaredoxins, encoded by GRX1 and GRX2, which are active as glutathione-dependent oxidoreductases. Our studies show that changes in the levels of glutaredoxins affect the resistance of yeast cells to oxidative stress induced by hydroperoxides. Elevating the gene dosage of GRX1 or GRX2 increases resistance to hydroperoxides including hydrogen peroxide, tert-butyl hydroperoxide and cumene hydroperoxide. The glutaredoxin-mediated resistance to hydroperoxides is dependent on the presence of an intact glutathione system, but does not require the activity of phospholipid hydroperoxide glutathione peroxidases (GPX1-3). Rather, the mechanism appears to be mediated via glutathione conjugation and removal from the cell because it is absent in strains lacking glutathione-S-transferases (GTT1, GTT2) or the GS-X pump (YCF1). We show that the yeast glutaredoxins can directly reduce hydroperoxides in a catalytic manner, using reducing power provided by NADPH, GSH, and glutathione reductase. With cumene hydroperoxide, high pressure liquid chromatography analysis confirmed the formation of the corresponding cumyl alcohol. We propose a model in which the glutathione peroxidase activity of glutaredoxins converts hydroperoxides to their corresponding alcohols; these can then be conjugated to GSH by glutathione-S-transferases and transported into the vacuole by Ycf1.
引用
收藏
页码:16712 / 16717
页数:6
相关论文
共 47 条
[31]   The molecular defences against reactive oxygen species in yeast [J].
MoradasFerreira, P ;
Costa, V ;
Piper, P ;
Mager, W .
MOLECULAR MICROBIOLOGY, 1996, 19 (04) :651-658
[32]   Purification and characterization of Acr2p, the Saccharomyces cerevisiae arsenate reductase [J].
Mukhopadhyay, R ;
Shi, J ;
Rosen, BP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (28) :21149-21157
[33]   ISOLATION AND IDENTIFICATION OF ERYTHROASCORBIC ACID IN SACCHAROMYCES-CEREVISIAE AND LYPOMYCES-STARKEYI [J].
NICK, JA ;
LEUNG, CT ;
LOEWUS, FA .
PLANT SCIENCE, 1986, 46 (03) :181-187
[34]   Purification, cloning and expression of dehydroascorbic acid-reducing activity from human neutrophils: Identification as glutaredoxin [J].
Park, JB ;
Levine, M .
BIOCHEMICAL JOURNAL, 1996, 315 :931-938
[35]   The genetics of disulfide bond metabolism [J].
Rietsch, A ;
Beckwith, J .
ANNUAL REVIEW OF GENETICS, 1998, 32 :163-184
[36]  
Rodríguez-Manzaneque MT, 1999, MOL CELL BIOL, V19, P8180
[37]   Glutathione, oxidative stress and neurodegeneration [J].
Schulz, JB ;
Lindenau, J ;
Seyfried, J ;
Dichgans, J .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2000, 267 (16) :4904-4911
[38]   STRESS TOLERANCE AND MEMBRANE LIPID UNSATURATION IN SACCHAROMYCES-CEREVISIAE GROWN AEROBICALLY OR ANAEROBICALLY [J].
STEELS, EL ;
LEARMONTH, RP ;
WATSON, K .
MICROBIOLOGY-SGM, 1994, 140 :569-576
[39]   Disulfide bond formation in the Escherichia coli cytoplasm:: an in vivo role reversal for the thioredoxins [J].
Stewart, EJ ;
Åslund, F ;
Beckwith, J .
EMBO JOURNAL, 1998, 17 (19) :5543-5550
[40]  
SZCZYPKA MS, 1994, J BIOL CHEM, V269, P22853