Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1783, Issue 2, Pages 237-245Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2007.08.008
Keywords
aldo-keto reductase; inositol auxotrophy; oxidative stress; heat shock sensitivity
Categories
Funding
- NEI NIH HHS [R01 EY005856-23, P30 EY002687-28, EY02687, R01 EY005856-22, P30 EY002687-29, P30 EY002687, EY05856, R01 EY005856] Funding Source: Medline
Ask authors/readers for more resources
A large family of aldo-keto reductases with similar kinetic and structural properties but unknown physiological roles is expressed in the yeast Saccharomyces cerevisiae. Strains with one or two AKR genes disrupted have apparently normal phenotypes, but disruption of at least three AKR genes results in a heat shock phenotype and slow growth in inositol-deficient culture medium (Ino(-)). The present study was carried out to identify metabolic or signaling defects that may underlie phenotypes that emerge in AKR deficient strains. Here we demonstrate that pretreatment of a pentuple AKR null mutant with the anti-oxidative agent N-acetyl-cysteine rescues the heat shock phenotype. This indicates that AKR gene disruption may be associated with defects in oxidative stress response. We observed additional markers of oxidative stress in AKR-deficient strains, including reduced glutathione levels, constitutive nuclear localization of the oxidation-sensitive transcription factor Yap 1 and upregulation of a set of Yap 1 target genes whose function as a group is primarily involved in response to oxidative stress and redox balance. Genetic analysis of the Ino(-) phenotype of the null mutants showed that defects in transcriptional regulation of the INO1, which encodes for inositol-1-phosphate synthase, can be rescued through ectopic expression of a functional INO1. Taken together, these results suggest potential roles for AKRs in oxidative defense and transcriptional regulation. (C) 2007 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available