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Journal of Neuroscience, Vol 5, 307-316, Copyright © 1985 by Society for Neuroscience
The effect of fibroblast growth factor on PC12 cells
A Togari, G Dickens, H Kuzuya and G Guroff
PC12 cells, which differentiate morphologically and biochemically into
sympathetic neuron-like cells when treated with nerve growth factor, also
respond to fibroblast growth factor. Some of the changes induced by
fibroblast growth factor are similar to those seen after nerve growth
factor treatment. Specifically, pituitary fibroblast growth factor causes
the formation of processes initially comparable to those produced by nerve
growth factor. However, in contrast to the outgrowth induced by nerve
growth factor, which continues for several days, the outgrowth of processes
induced by fibroblast growth factor ceases after about 3 days, even though
fresh fibroblast growth factor is added. After about 6 days the processes
induced by fibroblast growth factor have virtually disappeared. In this
regard the processes induced by fibroblast growth factor are very similar
to those induced by dibutyryl cyclic adenosine 3':5'-monophosphate
(dBcAMP). The addition of nerve growth factor and fibroblast growth factor
together appears to produce a synergistic effect on process formation, as
does the simultaneous addition of nerve growth factor and dBcAMP. Cells
pretreated (or primed) with nerve growth factor are able to regenerate
processes much more rapidly in the presence of nerve growth factor than
cells which have not been pretreated. When fibroblast growth factor is
added to cells primed with nerve growth factor, more rapid regeneration of
processes also occurs. The regeneration of neurites in response to either
factor is blocked by the addition of an inhibitor of methylation. The
process formation induced by fibroblast growth factor is preceded, as is
the outgrowth in response to nerve growth factor treatment, by an induction
of ornithine decarboxylase, a decrease in the phosphorylation of a specific
cytoplasmic protein, and an increase in the phosphorylation of a specific
non-histone nuclear protein. The effects of fibroblast growth factor and of
nerve growth factor on ornithine decarboxylase are additive. Fibroblast
growth factor does not cause an increase in the activity of
acetylcholinesterase; nerve growth factor does. Fibroblast growth factor
does not appear to be acting through the nerve growth factor receptor. The
binding of iodinated nerve growth factor to PC12 cells is specific and is
not inhibited by the presence of fibroblast growth factor. In addition,
anti-nerve growth factor serum does not interfere with the action of
fibroblast growth factor.(ABSTRACT TRUNCATED AT 400 WORDS)
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