Journal article
Glutathione dependent metabolism and detoxification of 4-hydroxy-2-nonenal
Free radical biology & medicine, Vol.11(4), pp.415-423
1991
DOI: 10.1016/0891-5849(91)90159-Z
PMID: 1797627
Abstract
The involvement of glutathione (GSH) dependent processes in the detoxification of 4-hydroxy-2-nonenal (4HNE) was investigated using Chinese hamster fibroblasts and clonogenic cell survival. GSH reacted, in a dose-dependent fashion, with 4HNE in phosphate buffer at pH 6.5, leading to the disappearance of 4HNE. The addition of glutathione transferase activity (GST) facilitated a more rapid disappearance of 4HNE but the reaction was still dependent on the concentration of GSH. When cell cultures were exposed to the reaction mixtures, 4HNE cytotoxicity was also reduced in a manner which was dependent on the concentration of GSH. When 2.16- or 1.08-mM GSH were incubated in phosphate buffer with 1.08-mM 4HNE in the presence or absence of GST, then mixed with media and placed on cells for 1 h, the cytotoxicity associated with exogenous exposure to free 4HNE was abolished. GSH depletion (>90%) using buthionine sulfoximine (BSO) was accomplished in control (HA1) and H
2O
2-resistant variants derived from HA1. GSH depletion resulted in enhanced cytotoxicity of 4HNE in all cell lines. This BSO-induced sensitization to 4HNE cytotoxicity was accompanied by a significant reduction in the ability of cells to metabolize 4HNE. The magnitude of the sensitization to 4HNE toxicity caused by GSH depletion was similar to the magnitude of the reduction in the ability of cells to metabolize 4HNE. These results support the hypothesis that GHS and GST provide a biologically significant pathway for protection against aldehydic by-products of lipid peroxidation.
Details
- Title: Subtitle
- Glutathione dependent metabolism and detoxification of 4-hydroxy-2-nonenal
- Creators
- Douglas R. Spitz - University of VirginiaShannon J. Sullivan - University of VirginiaRobert R. Malcolm - University of VirginiaRobert J. Roberts - University of Virginia
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.11(4), pp.415-423
- DOI
- 10.1016/0891-5849(91)90159-Z
- PMID
- 1797627
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 1991
- Academic Unit
- Stead Family Department of Pediatrics; Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984312972502771
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