Aim: 

Elucidation of the importance of glutathione and its nuclear pool in the proliferation of the cell lines of different inherent proliferative capacity, origin and differentiation level.

Methods: 

Glutathione determination by H.P.L.C. and enzymatic essay; telomerase activity by TRAP; glutathione distribution by CMFDA marking followed by confocal microscopy, cell cycle by flow cytometry and western blotting of regulatory proteins. Model: 3T3 fibroblasts, rat embryonic neural culture, MCF7 WT/MCF7 bcl2

Results: 

High level of reduced glutathione (GSH) coincided with the peak of telomerase activity and preceded the exponential phase of cell growth in all three cell types. The level of GSH corresponded to the intensity of the proliferation and clearly correlated with the level of DNA synthesis. Nuclear localization of GSH was observed before the exponential phase of cell growth in all three cell types, while the distribution was uniform throughout the cell when the proliferation stopped. The depletion of nuclear glutathione severely impaired cell cycle progression. Overexpression of bcl2 caused an early and striking increase of total cellular GSH, nuclear GSH and telomerase activity in MCF7 cells.

Conclusion: 

The level of GSH controls the cell proliferation, possibly by the modulation of redox sensitive cell cycle regulatory proteins and telomerase activity. Nuclear compartimentalization of GSH is a prerequisite for G1 to S phase transition and is facilitated by the nuclear Bcl-2. Our findings could have important implications in the study of pathophysiological processes in which the deregulation of cellular proliferation and telomerase activity has been demonstrated, such as aging and cancer.