UVC IRRADIATION INDUCES NEURITE OUTGROWTH IN PC12M3 CELLS VIA THE P38 MITOGEN-ACTIVATED PROTEIN KINASE AND TRANSCRIPTION FACTOR CREB PATHWAY

Abstract

We investigated cellular damage and differentiation of drug- hypersensitive PC12 mutant (PC12m3) cells caused by UVC irradiation. When PC12m3 cells were exposed to UVC irradiation, the frequency of neurite outgrowth rapidly increased in a dose-dependent manner in the presence of nerve growth factor (NGF). The frequency of neurite outgrowth was maximized at 40 J/m² of UVC irradiation, and this dose of UVC irradiation induced approximately 25-fold greater neurite outgrowth than that induced by NGF alone. However, the cells showed a strong toxicity at this dose of UVC irradiation. We also investigated whether the ability of UVC irradiation stimulus to induce neurite outgrowth of PC12m3 cells is a reflection of its effect on p38 MAPK activity. The results showed that p38 MAPK is strongly activated but that JNK and ERK were not so strongly activated in PC12m3 cells exposed to UVC irradiation of 40 J/m². Furthermore, UVC irradiation rapidly and strongly activated cyclic-AMP response element (CRE)-binding protein (CREB) in PC12m3 cells. CREB is a transcription factor that is the target of MAPK. These findings suggest that UVC irradiation induced neurite outgrowth through p38 MAPK and CREB pathways in PC12m3 cells.