Abstract
The previous reports have indicated the activation of the MAP kinase cascade and the induction of nitric oxide (NO) synthase (NOS) by low-dose irradiation in cell culture systems, suggesting that low-dose irradiation affects the cellular signal transduction. Nerve growth factor (NGF) is a neurotrophic factor that acts on peripheral nerve cells and induces the neurite extensions. Although the signal transductions of NGF are not completely known, it has been reported that the sustained activation of MAP kinase cascade is required in NGF-induced neurite extensions and that the NO-related pathway exists in the mechanisms by which the neurite extensions are induced. Taken together, it can be hypothesized that low-dose irradiation enhances the NGF-induced neurite extensions via the activation of MAP kinase and the generation of NO. To verify this hypothesis, the effect of low-dose irradiation on NGF-induced neurite extensions in PC12 cells was studied.
The PC12 cells were treated with NGF under the exposure of low-dose irradiation at low-dose rate. The irradiation enhanced temporally NGF-induced activation of MAP kinase cascade and then decreased the activity. Accordingly, the neurite extensions were slightly attenuated under the irradiation. The exposure of low-dose irradiation induced the increase in iNOS-expression. Furthermore, the NO-scavenger and the NOS inhibitors inhibited the irradiation-effect. These results suggest that low-dose irradiation, contrary to the hypothesis, attenuates NGF-induced neurite extension via the generation of NO.
