TY - JOUR
T1 - A timetable of events during programmed cell death induced by trophic factor withdrawal from neuronal PC12 cells
AU - Mesner, P. W.
AU - Epting, C. L.
AU - Hegarty, J. L.
AU - Green, S. H.
PY - 1995/11
Y1 - 1995/11
N2 - 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 lEGs 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 lEGs TIS7 and nur77 are not expressed during PCD, yielding a pattern distinct from that following other stimuli. An identical pattern of lEG expression occurs in non-neuronal PC12 cells deprived of serum, although expression begins at 10- 14 hr after serum withdrawal. A similar lEG 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 lEG expression described here should facilitate identification of intracellular regulatory signals active during PCD.
AB - 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 lEGs 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 lEGs TIS7 and nur77 are not expressed during PCD, yielding a pattern distinct from that following other stimuli. An identical pattern of lEG expression occurs in non-neuronal PC12 cells deprived of serum, although expression begins at 10- 14 hr after serum withdrawal. A similar lEG 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 lEG expression described here should facilitate identification of intracellular regulatory signals active during PCD.
KW - NGF
KW - PC12 cell
KW - Ras
KW - apoptosis
KW - immediate-early gene expression
KW - neurotrophic factor
KW - programmed cell death
KW - trophic factor
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U2 - 10.1523/jneurosci.15-11-07357.1995
DO - 10.1523/jneurosci.15-11-07357.1995
M3 - Article
C2 - 7472489
AN - SCOPUS:0028839253
SN - 0270-6474
VL - 15
SP - 7357
EP - 7366
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 11
ER -