Functional studies of aldo-keto reductases in Saccharomyces cerevisiae

被引:57
作者
Chang, Qing
Griest, Terry A.
Harter, Theresa M.
Petrash, J. Mark
机构
[1] Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2007年 / 1773卷 / 03期
关键词
aldo-keto reductase; aldose reductase; Saccharomyces cerevisiae; mutagenesis; heat shock;
D O I
10.1016/j.bbamcr.2006.10.009
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
We utilized the budding yeast Saccharomyces cerevisiae as a model to systematically explore physiological roles for yeast and mammalian aldo-keto reductases. Six open reading frames encoding putative aldo-keto reductases were identified when the yeast genome was queried against the sequence for human aldose reductase, the prototypical mammalian aldo-keto reductase. Recombinant proteins produced from five of these yeast open reading frames demonstrated NADPH-dependent reductase activity with a variety of aldehyde and ketone substrates. A triple aldo-keto reductase null mutant strain demonstrated a glucose-dependent heat shock phenotype which could be rescued by ectopic expression of human aldose reductase. Catalytically-inactive mutants of human or yeast aldo-keto reductases failed to effect a rescue of the heat shock phenotype, suggesting that the phenotype results from either an accumulation of one or more unmetabolized aldo-keto reductase substrates or a synthetic deficiency of aldo-keto reductase products generated in response to heat shock stress. These results suggest that multiple aldo-keto reductases fulfill functionally redundant roles in the stress response in yeast. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:321 / 329
页数:9
相关论文
共 56 条
[1]   Disruption of aldose reductase gene (Akr1b1) causes defect in urinary concentrating ability and divalent cation homeostasis [J].
Aida, K ;
Ikegishi, Y ;
Chen, J ;
Tawata, M ;
Ito, S ;
Maeda, S ;
Onaya, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 277 (02) :281-286
[2]   Cloning expression, and chaperone-like activity of human alpha A-crystallin [J].
Andley, UP ;
Mathur, S ;
Griest, TA ;
Petrash, JM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (50) :31973-31980
[3]   Structure of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase complexed with NADP [J].
Bennett, MJ ;
Schlegel, BP ;
Jez, JM ;
Penning, TM ;
Lewis, M .
BIOCHEMISTRY, 1996, 35 (33) :10702-10711
[4]   TYROSINE-48 IS THE PROTON DONOR AND HISTIDINE-110 DIRECTS SUBSTRATE STEREOCHEMICAL SELECTIVITY IN THE REDUCTION REACTION OF HUMAN ALDOSE REDUCTASE - ENZYME-KINETICS AND CRYSTAL-STRUCTURE OF THE Y48H MUTANT ENZYME [J].
BOHREN, KM ;
GRIMSHAW, CE ;
LAI, CJ ;
HARRISON, DH ;
RINGE, D ;
PETSKO, GA ;
GABBAY, KH .
BIOCHEMISTRY, 1994, 33 (08) :2021-2032
[5]  
Brachmann CB, 1998, YEAST, V14, P115
[7]  
Chang Q, 2004, ACS SYM SER, V865, P225
[8]   Aldo-keto reductases as modulators of stress response [J].
Chang, Q ;
Harter, TM ;
Rikimaru, LT ;
Petrash, JM .
CHEMICO-BIOLOGICAL INTERACTIONS, 2003, 143 :325-332
[9]   SGD:: Saccharomyces Genome Database [J].
Cherry, JM ;
Adler, C ;
Ball, C ;
Chervitz, SA ;
Dwight, SS ;
Hester, ET ;
Jia, YK ;
Juvik, G ;
Roe, T ;
Schroeder, M ;
Weng, SA ;
Botstein, D .
NUCLEIC ACIDS RESEARCH, 1998, 26 (01) :73-79
[10]   A PORTION OF RNA POLYMERASE-II MOLECULES HAS A COMPONENT ESSENTIAL FOR STRESS RESPONSES AND STRESS SURVIVAL [J].
CHODER, M ;
YOUNG, RA .
MOLECULAR AND CELLULAR BIOLOGY, 1993, 13 (11) :6984-6991