Protection against hydrogen peroxide cytotoxicity in Rat-1 fibroblasts provided by the oncoprotein Bcl-2: maintenance of calcium homoeostasis is secondary to the effect of Bcl-2 on cellular glutathione
| Autor: | Herbert de Groot, Ursula Rauen, Matthäus M. Rimpler, Tarik Möröy, Thorsten Schmidt |
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| Rok vydání: | 1999 |
| Předmět: |
Programmed cell death
Time Factors Fura-2 Cell Survival Glutathione reductase chemistry.chemical_element Biology Calcium Transfection GPX4 Biochemistry Cell Line Acetylcysteine chemistry.chemical_compound Adenosine Triphosphate medicine Animals Homeostasis Buthionine sulfoximine Buthionine Sulfoximine Molecular Biology Cell Death Hydrogen Peroxide Cell Biology Glutathione Fibroblasts Rats Cell biology Glucose Proto-Oncogene Proteins c-bcl-2 chemistry Aminoquinolines Pyrazoles Oxidation-Reduction Research Article medicine.drug |
| Zdroj: | Biochemical Journal. 340:291-297 |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | The oncoprotein Bcl-2 protects cells against apoptosis, but the exact molecular mechanism that underlies this function has not yet been identified. Studying H2O2-induced cell injury in Rat-1 fibroblast cells, we observed that Bcl-2 had a protective effect against the increase in cytosolic calcium concentration and subsequent cell death. Furthermore, overexpression of Bcl-2 resulted in an alteration of cellular glutathione status: the total amount of cellular glutathione was increased by about 60% and the redox potential of the cellular glutathione pool was maintained in a more reduced state during H2O2 exposure compared with non-Bcl-2-expressing controls. In our cytotoxicity model, disruption of cellular glutathione homoeostasis closely correlated with the pathological elevation of cytosolic calcium concentration. Stabilization of the glutathione pool by Bcl-2, N-acetylcysteine or glucose delayed the cytosolic calcium increase and subsequent cell death, whereas depletion of glutathione by DL-buthionine-(S,R)-sulphoximine, sensitized Bcl-2-transfected cells towards cytosolic calcium increase and cell death. We therefore suggest that the protection exerted by Bcl-2 against H2O2-induced cytosolic calcium elevation and subsequent cell death is secondary to its effect on the cellular glutathione metabolism. |
| Databáze: | OpenAIRE |
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