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**12** 

*Spain* 

**The Nuclear Compartmentation of Glutathione:** 

The oxidizing environment, shared by all aerobic organisms and crucial for their survival, poses a continuous threat to cellular structures all the living beings are made of. Structural proteins and lipids, and cellular membranes they compose, nucleic acids and enzymes that govern vital cellular processes are all susceptible to oxidative damage. Dealing with this inevitable and constant danger is one of the greatest challenges the living being with aerobic

Classical work of Kelvin Davies (Davies, 1999), more than ten years ago, showed that the cells show a whole range of responses to oxidative stress that depends on the intensity of the stress. Low level of hydrogen peroxide induced mitogenic responses and stimulation of proliferation; this observation was firstly reported by Oberly (Oberly et al., 1981) who have described that oxidative stimuli, such as superoxide and hydrogen peroxide, could activate signalling pathways that lead to proliferation. Davies et al. further assert that considerable increase in the oxidant concentrations caused temporary growth arrest which became permanent with a progressive increase. When high H2O2 concentrations were used, apoptosis took place and at very high oxidant levels the cells were killed by necrosis. A year later, (Pani et al., 2000) demonstrate a causal link between redox changes and growth control by cell density: they show that low level of oxygen species in the environment of proliferating cells was not only stimulating but necessary for the correct mitogenic signaling. This study was immediately followed by the work of Menon et al., 2003 who suggested that an oxidation event early in G1 phase may be a critical regulatory step in the progression of the cells into S phase. This lead to the development of the model of the "redox cycle within a cell cycle" proposed by the same group several years later (Menon &

According to this model, the transient change in ROS could modify the redox state of cell cycle regulatory proteins, at their critical cysteine residues, and thus determine progression or arrest in the proliferation. Antioxidant mechanism could scavenge ROS and reverse the process. In accordance to these reports, Barry Halliwell (Halliwell, 2007) draw a complete

**2. The implication of cellular redox balance in cell proliferation** 

**2.1 Reactive oxidative species in cell proliferation** 

**1. Introduction** 

metabolism has to meet.

Goswami 2007).

Jelena Markovic, Nancy Mora, Amparo Gimeno, Consuelo Burguete,

**Effect on Cell Cycle Progression** 

José Luis García-Gimenez and Federico V. Pallardó

*University of Valencia School of Medicine,* 

