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 el ucidated. While studying differentiation of PC12 cells we found that the si multaneous treatment of cells with NGF and IFN-gamma in serum-containing me dium resulted first in the extension of neurites and then apoptosis, On the contrary, in serum-free medium the cells underwent a more rapid neuronal d ifferentiation. Only the doses of NGF which induced the outgrowth of neurit es from the cells were able to induce rapid cell death in combined treatmen t. When the cells were treated subsequently with NGF and IFN-gamma, the ind uction of death was observed with NGF posttreatment, but not with NGF pretr eatment, Relying on these alternative biological responses, we studied the changes in 2-5A synthetase activity and its 43 kDa isoform expression in th e course of differentiation and death of PC12 cells, The results of the pre sent work showed that NGF-induced differentiation of the cells did not evok e any increase in 2-5A synthetase activity or any increase in the expressio n of its 43 kDa isoform. Moreover, the obtained results demonstrated that N GF could not significantly affect the IFN-induced signalling pathway leadin g to the activation of 2-5A synthetase gene, at least regarding the studied enzyme activity. (C) 2000 Academic Press.