Martin, Hans-Joerg and Ziemba, Marta and Kisiela, Michael and Botella, Jose A. and Schneuwly, Stephan and Maser, Edmund (2011) The Drosophila carbonyl reductase sniffer is an efficient 4-oxonon-2-enal (4ONE) reductase. CHEMICO-BIOLOGICAL INTERACTIONS, 191 (1-3). pp. 48-54. ISSN 0009-2797, 1872-7786
Full text not available from this repository. (Request a copy)Abstract
Studies with the fruit-fly Drosophila melanogaster demonstrated that the enzyme sniffer prevented oxidative stress-induced neurodegeneration. Mutant flies overexpressing sniffer had significantly extended life spans in a 99.5% oxygen atmosphere compared to wild-type flies. However, the molecular mechanism of this protection remained unclear. Sequence analysis and database searches identified sniffer as a member of the short-chain dehydrogenase/reductase superfamily with a 27.4% identity to the human enzyme carbonyl reductase type I (CBR1). As CBR1 catalyzes the reduction of the lipid peroxidation products 4HNE and 4ONE, we tested whether sniffer is able to metabolize these lipid derived aldehydes by carbonyl reduction. To produce recombinant enzyme, the coding sequence of sniffer was amplified from a cDNA-library, cloned into a bacterial expression vector and the His-tagged protein was purified by Ni-chelate chromatography. We found that sniffer catalyzed the NADPH-dependent carbonyl reduction of 4ONE (K-m = 24 +/- 2 mu M, k(cat) = 500 +/- 10 min(-1), k(cat)/K-m = 350 s(-1) mM(-1)) but not that of 4HNE. The reaction product of 4ONE reduction by sniffer was mainly 4HNE as shown by HPLC- and GC/MS analysis. Since 4HNE, though still a potent electrophile, is less neurotoxic and protein reactive than 4ONE, one mechanism by which sniffer exerts its neuroprotective effects in Drosophila after oxidative stress may be enzymatic reduction of 4ONE. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LIPID-PEROXIDATION PRODUCTS; OXIDATIVE STRESS; NEURODEGENERATION; MALONALDEHYDE; MELANOGASTER; SUPERFAMILY; PROTEINS; MODEL; Sniffer; Carbonyl reductase; 4HNE; 4ONE; Toxic aldehydes; Lipid peroxidation |
| Subjects: | 500 Science > 590 Zoological sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie > Entwicklungsbiologie (Prof. Dr. Stephan Schneuwly) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jun 2020 07:48 |
| Last Modified: | 15 Jun 2020 07:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20796 |
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