Cell cycle blockers mimosine, ciclopirox, and deferoxamine prevent the death of PC12 cells and postmitotic sympathetic neurons after removal of trophic support

In the present study, we tested whether apoptotic neuronal death caused by withdrawal of trophic support might be prevented by agents that block cell cycle progression. We used three complementary model systems that exhibit apoptotic death: dividing PC12 cells deprived of nerve growth factor (NGF);...

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Bibliographic Details
Published in:The Journal of neuroscience 1996-02, Vol.16 (3), p.1150-1162
Main Authors: Farinelli, SE, Greene, LA
Format: Article
Language:English
Subjects:
Animals
Aphidicolin - pharmacology
Apoptosis - drug effects
Cell Cycle - drug effects
Cell Division - drug effects
Cyclic AMP - analogs & derivatives
Cyclic AMP - pharmacology
Deferoxamine - pharmacology
G1 Phase - drug effects
Mimosine - pharmacology
Mitosis
Nerve Growth Factors - pharmacology
Neurons - drug effects
Nocodazole - pharmacology
PC12 Cells - drug effects
Pyridones - pharmacology
Rats
Superior Cervical Ganglion - cytology
Teniposide - pharmacology
Thionucleotides - pharmacology
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Summary:In the present study, we tested whether apoptotic neuronal death caused by withdrawal of trophic support might be prevented by agents that block cell cycle progression. We used three complementary model systems that exhibit apoptotic death: dividing PC12 cells deprived of nerve growth factor (NGF); and primary cultures of postmitotic sympathetic neurons deprived of NGF. We show that cell death in each case can be suppressed by treatment with the G1/S blockers mimosine, ciclopirox, and deferoxamine at concentrations that correlate with their abilities to block PC12 cell proliferation. In contrast, agents that block cell cycle progression in the S-, G2-, or M-phase do not prevent cell death. These observations support the hypothesis that removal of trophic support from dividing or postmitotic neuronal cells provokes their apoptotic death by causing them either to proceed through or to attempt to re-enter an uncoordinated and consequently fatal cell cycle. Moreover, the data suggest that simply blocking the cycle at any point is not protective but, rather, that it is necessary to block at specific "safe" points. This study defines a safe point in the cell cycle before the G1/S transition that is demarcated by the action of these three agents.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.16-03-01150.1996