Abstract |
Aldehyde dehydrogenase (ALDH) enzymes are responsible for the metabolism of aldehydes, including acetaldehyde (AA), and are linked to disease. We describe a method to study ALDH activity in cell cultures involving the measurement of AA concentrations in the gas/vapour phase. This has been achieved using selected ion flow tube mass spectrometry (SIFT-MS), developed for the rapid quantification of trace gases in humid media. Human cells of the hepG2 hepatocellular carcinoma cell line and primary bone marrow-derived mesenchymal stem cells (hMSCs) depleted AA from the culture media, but the application of ALDH inhibitors diethylaminobenzaldehyde ( DEAB) and disulfiram (DSF), suppressed this depletion or in some cases resulted in elevated AA concentrations. Further, the cells were shown to reduce the dimethyl sulphoxide ( DMSO) to dimethyl sulphide, which is mediated by methionine sulfoxide reductase A (MsrA) enzymes. Interestingly, this process was also inhibited by DEAB and DSF. The results of this study indicate that SIFT-MS gas phase analysis could be applied to the study of volatile metabolites of intracellular enzyme reactions, this having potential utility in disease research and drug discovery.
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Authors | Thomas W E Chippendale, Bin Hu, Alicia J El Haj, David Smith |
Journal | The Analyst
(Analyst)
Vol. 137
Issue 20
Pg. 4677-85
(Oct 21 2012)
ISSN: 1364-5528 [Electronic] England |
PMID | 22930361
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amino Acids
- Biomarkers
- Gases
- Sulfides
- Aldehyde Dehydrogenase
- Methionine Sulfoxide Reductases
- dimethyl sulfide
- Disulfiram
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Topics |
- Aldehyde Dehydrogenase
(antagonists & inhibitors, metabolism)
- Amino Acids
(analysis)
- Biomarkers
(analysis)
- Cell Survival
(drug effects)
- Cells, Cultured
- Disulfiram
(pharmacology)
- Gases
(chemistry)
- Hep G2 Cells
- Humans
- Mass Spectrometry
- Mesenchymal Stem Cells
(metabolism)
- Methionine Sulfoxide Reductases
(antagonists & inhibitors, metabolism)
- Sulfides
(analysis)
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