Mouse aldo-keto reductase AKR7A5 protects V79 cells against 4-hydroxynonenal-induced apoptosis
| Autor: | Elizabeth M. Ellis, Dan Li, Rachel Gardner, Gail McGarvie, Alison Hinshelwood |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Programmed cell death
Blotting Western Aldo-Keto Reductases Tetrazolium Salts Apoptosis Cysteine Proteinase Inhibitors Biology Reductase Transfection Toxicology Cell Line 4-Hydroxynonenal Mice chemistry.chemical_compound Aldehyde Reductase Cricetinae Animals MTT assay Cytotoxicity Aldehydes Aldo-keto reductase Dose-Response Relationship Drug Caspase 3 Mutagenicity Tests Fibroblasts Molecular biology Alcohol Oxidoreductases Thiazoles chemistry Cell culture Caspases Lipid Peroxidation |
| Zdroj: | Toxicology. 226:172-180 |
| ISSN: | 0300-483X |
| DOI: | 10.1016/j.tox.2006.06.013 |
| Popis: | We have developed transgenic Chinese hamster V79 cell lines in order to examine the potential for a mouse aldo-keto reductase, AKR7A5, to protect against the toxicity of 4-hydroxynonenal (4-HNE) and related toxic aldehydes. Stable expression of mouse AKR7A5 in V79 cells conferred four-fold increased resistance to 4-HNE cytotoxicity using the MTT assay compared to empty vector-transfected V79 cells. Cells expressing AKR7A5 showed a decrease in mutation rate compared to control cells in the presence of 4-HNE as measured by HGPRT mutagenicity assay. Furthermore, the cells expressing AKR7A5 showed decreased 4-HNE-induced caspase-3 activity in both a time and dose-dependent manner compared to control cells. These results show that in V79 cells 4-HNE mediates apoptosis via caspase-3 activation and that the AKR7A5 enzyme is able to metabolize 4-HNE in cells, thereby attenuating 4-HNE-induced apoptosis. AKR7A isozymes may therefore be important in protecting against toxic aldehydes derived from lipid peroxidation in vivo. |
| Databáze: | OpenAIRE |
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