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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Nomura, Michiyo Takagi, Hiroshi |
| Description | Author Affiliation: Nomura M ( Department of Bioscience, Fukui Prefectural University, Fukui 910-1195, Japan.); |
| Abstract | The MPR1 gene, which is found in the Sigma1278b strain but is not present in the sequenced laboratory strain S288C, of the budding yeast Saccharomyces cerevisiae encodes a previously uncharacterized N-acetyltransferase that detoxifies the proline analogue azetidine-2-carboxylate (AZC). However, it is unlikely that AZC is a natural substrate of Mpr1 because AZC is found only in some plant species. In our search for the physiological function of Mpr1, we found that mpr1-disrupted cells were hypersensitive to oxidative stresses and contained increased levels of reactive oxygen species (ROS). In contrast, overexpression of MPR1 leads to an increase in cell viability and a decrease in ROS level after oxidative treatments. These results indicate that Mpr1 can reduce intracellular oxidation levels. Because put2-disrupted yeast cells lacking Delta(1)-pyrroline-5-carboxylate (P5C) dehydrogenase have increased ROS, we examined the role of Mpr1 in put2-disrupted strains. When grown on media containing urea and proline as the nitrogen source, put2-disrupted cells did not grow as well as WT cells and accumulated intracellular levels of P5C that were first detected in yeast cells and ROS. On the other hand, put2-disrupted cells that overexpressed MPR1 had considerably lower ROS levels. In vitro studies with bacterially expressed Mpr1 demonstrated that Mpr1 can acetylate P5C, or, more likely, its equilibrium compound glutamate-gamma-semialdehyde, at neutral pH. These results suggest that the proline catabolism intermediate P5C is toxic to yeast cells because of the formation of ROS, and Mpr1 regulates the ROS level under P5C-induced oxidative stress. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 34 |
| Volume Number | 101 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2004-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Acetyltransferases Metabolism Oxidative Stress Proline Reactive Oxygen Species Saccharomyces Cerevisiae Proteins Acetylation Genetics Azetidinecarboxylic Acid Molecular Sequence Data Molecular Structure Oxidation-Reduction Chemistry Proline Oxidase Pyrroline Carboxylate Reductases Saccharomyces Cerevisiae Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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