Expression and activity of 2-5A synthetase in the course of differentiation and apoptosis of PC12 cells.

The role of IFN-induced 2-5A system in cell differentiation has not been elucidated. While studying differentiation of PC12 cells we found that the simultaneous treatment of cells with NGF and IFN-gamma in serum-containing medium resulted first in the extension of neurites and then apoptosis. On the contrary, in serum-free medium the cells underwent a more rapid neuronal differentiation. Only the doses of NGF which induced the outgrowth of neurites from the cells were able to induce rapid cell death in combined treatment. When the cells were treated subsequently with NGF and IFN-gamma, the induction of death was observed with NGF post-treatment, but not with NGF pretreatment. Relying on these alternative biological responses, we studied the changes in 2-5A synthetase activity and its 43 kDa isoform expression in the course of differentiation and death of PC12 cells. The results of the present work showed that NGF-induced differentiation of the cells did not evoke any increase in 2-5A synthetase activity or any increase in the expression of its 43 kDa isoform. Moreover, the obtained results demonstrated that NGF could not significantly affect the IFN-induced signalling pathway leading to the activation of 2-5A synthetase gene, at least regarding the studied enzyme activity.