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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
Journal of Neuroscience 1 November 1995, 15 (11) 7357-7366; DOI: https://doi.org/10.1523/JNEUROSCI.15-11-07357.1995
PW Mesner
Department of Biological Sciences, University of Iowa, Iowa City 52242– 1324, USA.
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CL Epting
Department of Biological Sciences, University of Iowa, Iowa City 52242– 1324, USA.
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JL Hegarty
Department of Biological Sciences, University of Iowa, Iowa City 52242– 1324, USA.
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SH Green
Department of Biological Sciences, University of Iowa, Iowa City 52242– 1324, USA.
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Abstract

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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The Journal of Neuroscience: 15 (11)
Journal of Neuroscience
Vol. 15, Issue 11
1 Nov 1995
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A timetable of events during programmed cell death induced by trophic factor withdrawal from neuronal PC12 cells
PW Mesner, CL Epting, JL Hegarty, SH Green
Journal of Neuroscience 1 November 1995, 15 (11) 7357-7366; DOI: 10.1523/JNEUROSCI.15-11-07357.1995

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A timetable of events during programmed cell death induced by trophic factor withdrawal from neuronal PC12 cells
PW Mesner, CL Epting, JL Hegarty, SH Green
Journal of Neuroscience 1 November 1995, 15 (11) 7357-7366; DOI: 10.1523/JNEUROSCI.15-11-07357.1995
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