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Journal of Neuroscience, Vol 15, 7357-7366, Copyright © 1995 by Society for Neuroscience
A timetable of events during programmed cell death induced by trophic factor withdrawal from neuronal PC12 cells
PW Mesner, CL Epting, JL Hegarty and SH Green
Department of Biological Sciences, University of Iowa, Iowa City 52242- 1324, USA.
We describe a timetable of events during programmed cell death (PCD) in
neuronal PC12 cells, specifically, Ras signaling, immediate-early gene
(IEG) expression, DNA fragmentation and commitment to PCD. Commitment
occurs over a period from 10-20 hr after NGF withdrawal. Ras signaling
declines rapidly after NGF removal, reaching minimal levels within 2-4 hr,
well before the onset of commitment. DNA fragmentation, detected by TUNEL
reaction, begins about 24 hr after NGF withdrawal, well after all cells are
committed, but coincident with the onset of cell dissolution previously
determined by trypan blue exclusion (Mesner et al., 1992). Among the IEGs
studied here, c-jun and TIS21 are expressed within 6 hr after NGF
withdrawal. Expression of c-fos, egr-1, and TIS11 does not begin until 20
hr after NGF withdrawal. IEG expression generally ends by 24 hr after NGF
withdrawal. The IEGs TIS7 and nur77 are not expressed during PCD, yielding
a pattern distinct from that following other stimuli. An identical pattern
of IEG expression occurs in non- neuronal PC12 cells deprived of serum,
although expression begins at 10- 14 hr after serum withdrawal. A similar
IEG expression pattern was observed in Rat-1 fibroblasts, with various
genes expressed 6-18 hr after serum withdrawal. In none of these cell types
did expression of the stress-related gene Hsp70 change following trophic
factor withdrawal. The distinctive pattern of IEG expression described here
should facilitate identification of intracellular regulatory signals active
during PCD.
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