CYCLOOXYGENASE-1 BEHAVES AS A DELAYED-RESPONSE GENE IN PC12 CELLS DIFFERENTIATED BY NERVE GROWTH-FACTOR

Treatment of PC12 cells with nerve growth factor (NGF) results in a di fferentiation program characterized by expression of immediate early a nd delayed response genes. In this program, morphological changes such as neurite extension are accompanied by phenotypic changes in enzyme expression, including an in creased capacity for prostaglandin synthes is. Cyclooxygenase (COX), the enzyme responsible for prostanoid produc tion, exists as two isoforms: constitutive COX-1 and inducible COX-2. We report that COX-1 behaves as a delayed response gene in PC12 cells exposed to NGF. Six hours following NGF treatment, COX-1 mRNA levels w ere elevated in PC12 cells, reaching nearly B-fold above basal levels at 12 h. This increase was blocked by cycloheximide and was accompanie d by concomitant increases in COX-1 protein and enzyme activity, COX-1 protein remained elevated for at least 10 days and localized to the c ytoplasm and neurites of NGF-differentiated PC12 cells. Moreover, basi c fibroblast growth factor, but not epidermal growth factor, caused si milar increases in COX-1, which is consistent with expression characte ristics of other delayed response genes in PC12 cells. This is the fir st example of neurotrophic factor regulation of cyclooxygenase and may have important implications for determination of the differentiated p henotype in PC12 cells.