The depletion of nuclear glutathione impairs cell proliferation in 3t3 fibroblasts

Glutathione is considered essential for survival in mammalian cells and yeast but not in prokaryotic cells. The presence of a nuclear pool of glutathione has been demonstrated but its role in cellular proliferation and differentiation is still a matter of debate. We have studied proliferation of 3T3...

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Published in:PloS one 2009-07, Vol.4 (7), p.e6413
Main Authors: Markovic, Jelena, Mora, Nancy J, Broseta, Ana M, Gimeno, Amparo, de-la-Concepción, Noelia, Viña, José, Pallardó, Federico V
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Antioxidants
Biochemistry
Biochemistry/Cell Signaling and Trafficking Structures
Buthionine sulfoximine
Buthionine Sulfoximine - pharmacology
Cell Biology/Cell Growth and Division
Cell cycle
Cell differentiation
Cell growth
Cell Nucleus - metabolism
Cell proliferation
Cell Proliferation - drug effects
Cell survival
Cells (Biology)
Cytoplasm
Deoxyribonucleic acid
Depletion
Diethyl maleate
DNA
Fibroblasts
Fibroblasts - cytology
Fibroblasts - drug effects
Gene expression
Glutathione
Glutathione - metabolism
Glutathione Reductase - metabolism
Glutathione Transferase - metabolism
Growth factors
Maleates - pharmacology
Mammalian cells
Medicine
Mice
Microscopy, Confocal
Molecular weight
Oxidative stress
Physiology
Rodents
Studies
Thiols
Trends
Yeast
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description Glutathione is considered essential for survival in mammalian cells and yeast but not in prokaryotic cells. The presence of a nuclear pool of glutathione has been demonstrated but its role in cellular proliferation and differentiation is still a matter of debate. We have studied proliferation of 3T3 fibroblasts for a period of 5 days. Cells were treated with two well known depleting agents, diethyl maleate (DEM) and buthionine sulfoximine (BSO), and the cellular and nuclear glutathione levels were assessed by analytical and confocal microscopic techniques, respectively. Both agents decreased total cellular glutathione although depletion by BSO was more sustained. However, the nuclear glutathione pool resisted depletion by BSO but not with DEM. Interestingly, cell proliferation was impaired by DEM, but not by BSO. Treating the cells simultaneously with DEM and with glutathione ethyl ester to restore intracellular GSH levels completely prevented the effects of DEM on cell proliferation. Our results demonstrate the importance of nuclear glutathione in the control of cell proliferation in 3T3 fibroblasts and suggest that a reduced nuclear environment is necessary for cells to progress in the cell cycle.
doi_str_mv 10.1371/journal.pone.0006413
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subjects 3T3 Cells
Animals
Antioxidants
Biochemistry
Biochemistry/Cell Signaling and Trafficking Structures
Buthionine sulfoximine
Buthionine Sulfoximine - pharmacology
Cell Biology/Cell Growth and Division
Cell cycle
Cell differentiation
Cell growth
Cell Nucleus - metabolism
Cell proliferation
Cell Proliferation - drug effects
Cell survival
Cells (Biology)
Cytoplasm
Deoxyribonucleic acid
Depletion
Diethyl maleate
DNA
Fibroblasts
Fibroblasts - cytology
Fibroblasts - drug effects
Gene expression
Glutathione
Glutathione - metabolism
Glutathione Reductase - metabolism
Glutathione Transferase - metabolism
Growth factors
Maleates - pharmacology
Mammalian cells
Medicine
Mice
Microscopy, Confocal
Molecular weight
Oxidative stress
Physiology
Rodents
Studies
Thiols
Trends
Yeast
title The depletion of nuclear glutathione impairs cell proliferation in 3t3 fibroblasts
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