| A decrease in intracellular glutathione concentration precedes the onset of apoptosis in murine thymocytes. | |
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MedLine Citation:
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PMID: 8549589 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Free radical damage has been implicated in the induction of apoptosis in some cells. We investigated whether the status of a cell's oxidant defence system is involved in the signalling pathways triggering apoptosis. We used three unrelated agents, dexamethasone, thapsigargin and gliotoxin to induce apoptosis in thymocytes from 10-day-old BALB/c mice. With all stimuli there was a correlation between the percentage of cells undergoing apoptosis (as measured with propidium iodide DNA staining) and the percentage of cells with lowered [GSH]i. Treatment with either 1 mM reduced glutathione or 10 nM thapsigargin inhibited dexamethasone-induced apoptosis in thymocytes at 6 h, as well as the rise in the percentage of cells with lowered [GSH]i that normally accompanied the onset of apoptosis. Furthermore, following treatment of thymocytes with oxidized glutathione, a normal product of the action of the cell's oxidant defence system, high levels of apoptosis were observed. This suggested that the onset of apoptosis was not simply the result of a loss of GSH from the cytosol. From our evidence we suggest that a decrease in [GSH]i, or an increase in [GSSG]i or perhaps a change in the ratio of [GSH]i to [GSSG]i constitutes a trigger for apoptosis. |
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Authors:
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J P Beaver; P Waring |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: European journal of cell biology Volume: 68 ISSN: 0171-9335 ISO Abbreviation: Eur. J. Cell Biol. Publication Date: 1995 Sep |
Date Detail:
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Created Date: 1996-02-22 Completed Date: 1996-02-22 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7906240 Medline TA: Eur J Cell Biol Country: GERMANY |
Other Details:
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Languages: eng Pagination: 47-54 Citation Subset: IM |
Affiliation:
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Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra/Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis / drug effects, physiology* Calcium-Transporting ATPases / antagonists & inhibitors Dexamethasone / pharmacology Enzyme Inhibitors / pharmacology Gliotoxin / pharmacology Glucocorticoids / pharmacology Glutathione / analogs & derivatives, metabolism* Glutathione Disulfide Mice Oxidation-Reduction Terpenes / pharmacology Thapsigargin Thymus Gland / cytology, drug effects, metabolism* Time Factors |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Glucocorticoids; 0/Terpenes; 27025-41-8/Glutathione Disulfide; 50-02-2/Dexamethasone; 67-99-2/Gliotoxin; 67526-95-8/Thapsigargin; 70-18-8/Glutathione; EC 3.6.1.8/Calcium-Transporting ATPases |
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