title: The depletion of nuclear glutathione impairs cell proliferation in 3t3 fibroblasts.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Valencia, Valencia, Spain.
authors.forename: Jelena
authors.initials: J
authors.lastname: Markovic
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Mora
authors.forename: Ana M
authors.initials: AM
authors.lastname: Broseta
authors.forename: Amparo
authors.initials: A
authors.lastname: Gimeno
authors.forename: Noelia
authors.initials: N
authors.lastname: de-la-Concepción
authors.forename: José
authors.initials: J
authors.lastname: Viña
authors.forename: Federico V
authors.initials: FV
authors.lastname: Pallardó
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D008298:Maleates / Q000494:pharmacology; D051379:Mice; D018613:Microscopy, Confocal
chemical_list: D008298:Maleates; D019328:Buthionine Sulfoximine; D005980:Glutathione Reductase; D005982:Glutathione Transferase; C014476:diethyl maleate; D005978:Glutathione