EPIDERMAL GROWTH-FACTOR PREVENTS OXYGEN-TRIGGERED APOPTOSIS AND INDUCES SUSTAINED SIGNALING IN CULTURED RAT CEREBRAL CORTICAL-NEURONS

Epidermal growth factor (EGF), a conventional mitogenic factor, acts a s a neurotrophic factor on several types of neurons in the central ner vous system. We found that EGF prevented the death of rat cerebral cor tical neurons cultured in a 50% oxygen atmosphere. This high-oxygen-tr iggered cell death showed features of apoptotic cell death, which was blocked by inhibitors of RNA or protein synthesis. EGF prevented the o xygen-induced death of the cultured cortical neurons in a dose-depende nt manner. Basic fibroblast growth factor (bFGF) also prevented this c ell death, although there was no apparent additive effect of EGF and b FGF. Among the cultured cortical neurons, we observed neurons possessi ng the EGF receptor and cells expressing c-Fos protein in response to EGF. The cortical neurons were cultured in the presence of cytosine ar abinoside, and the number of glial fibrillary acidic protein-positive astroglial cells was <0.5% of that of the corresponding microtubule-as sociated protein 2-positive neurons. Therefore, the effect of EGF on t he cultured cortical neurons is thought to be due to a direct action. We also examined EGF-induced signalling in the cultured cortical neuro ns. We found that EGF induced the sustained tyrosine phosphorylation o f the EGF receptor and sustained the activation of mitogen-activated p rotein kinase in the cultured cortical neurons. We suggest that EGF ma y exert the survival effect through the prolonged activation of the EG F signalling.