Cell signalling and the glutathione redox system
Section snippets
Intracellular redox environment
What does intracellular redox environment depend on? The intracellular redox state is determined by the contribution of different redox couples. Each couple can exchange electrons in such a way that, by giving or accepting reducing equivalents, may represent good cofactors in redox enzymatic reactions. The relative amount of reduced and oxidised form of each system may determine changes in cellular redox state by shifting this value towards oxidising or reducing conditions. The three most
Glutathione, thiol redox state and the regulation of cellular processes
Several evidence of the last few years supported the idea that GSH decrease is often associated with the apoptotic program. In our laboratory we demonstrated the fundamental role that GSH plays in the commitment of programmed cell death [20], [21], [22]. In fact, we evidenced that, upon apoptotic stimulus, cytochrome c release from mitochondria occurs in concomitance with a massive extrusion of GSH through specific membrane translocators [20]. This phenomenon seemed to be one of the first event
Extracellular environment and intracellular redox response
The extracellular environment can dialogue with the intracellular compartments in a wide range of modalities. External molecules such as lipophylic hormones or esterified compounds, can freely cross the plasma membrane owing to their chemical nature and act inside the cell without restrictions. On the other hand, hydrophylic molecules can enter the cell only through the action of specific channels or ATP-dependent pumps. Finally, there are compounds which are totally membrane-impermeable but
Conclusion and hypotheses for future work
Recently, we have tried to modulate the intracellular redox environment of eukaryotic cells by treating a human promonocytic cell line, U937, with glutathione disulphide. This compound is a nonpermeable agent usually present at very low concentration both inside and outside the cell, since it is efficiently reduced back to GSH by the activity of GSSG-reductase. However, under an oxidative burst, GSSG can be produced at high rate and it can be extruded from cells into the extracellular milieu,
Acknowledgements
This work was partially supported by MURST “Cofinanziamento 2000”, CNR and Ministero della Sanità “Progetto di Ricerca Finalizzata”.
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