Md. Kaplan et al., CYCLOOXYGENASE-1 BEHAVES AS A DELAYED-RESPONSE GENE IN PC12 CELLS DIFFERENTIATED BY NERVE GROWTH-FACTOR, The Journal of biological chemistry, 272(30), 1997, pp. 18534-18537
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.