Apoptosis of central and peripheral neurons can be prevented with cyclin-dependent kinase/mitogen-activated protein kinase inhibitors.

Details

Serval ID
serval:BIB_67F250802B20
Type
Article: article from journal or magazin.
Collection
Publications
Title
Apoptosis of central and peripheral neurons can be prevented with cyclin-dependent kinase/mitogen-activated protein kinase inhibitors.
Journal
Journal of Neurochemistry
Author(s)
Maas J.W., Horstmann S., Borasio G.D., Anneser J.M., Shooter E.M., Kahle P.J.
ISSN
0022-3042 (Print)
ISSN-L
0022-3042
Publication state
Published
Issued date
1998
Volume
70
Number
4
Pages
1401-1410
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Abstract
Previous studies have indicated that certain members of the cyclin-dependent kinase/mitogen-activated protein kinase superfamily are involved in apoptosis of neuronal cells. Here, we have examined programmed cell death induced by withdrawal of neurotrophic support from CNS (rat retinal) and PNS (chick sympathetic, sensory, and ciliary) neurons. All four neuron types were equally rescued by the purine analogues olomoucine and roscovitine. Olomoucine inhibits multiple cyclin-dependent and mitogen-activated protein kinases with similar potency. Roscovitine is a more selective cyclin-dependent kinase inhibitor; but, so is butyrolactone I, which did not prevent retinal ganglion cell death. The specific p38MAPK inhibitor SB-203580 did not prevent apoptosis in retinal ganglion cells. Death of these cells in the absence of neurotrophic factors was accompanied by morphological changes indicative of apoptosis, including nuclear condensation and fragmentation. Treatment with olomoucine or roscovitine not only prevented these apoptotic changes in retinal ganglion cells but also blocked neurite outgrowth. The survival-promoting activity of olomoucine correlated with its in vitro IC50 for c-Jun N-terminal kinase-1 and its potency to repress c-jun induction in live PC12 cells. Roscovitine was more potent in rescuing neurons than in inhibiting Jun kinase. Thus, the antiapoptotic action of roscovitine might be due to inhibition of additional kinases.
Keywords
Animals, Apoptosis/drug effects, Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors, Cell Nucleus/drug effects, Chick Embryo, Cyclin-Dependent Kinases/antagonists & inhibitors, Ganglia/cytology, Ganglia/drug effects, Kinetin, Neurons/drug effects, Proto-Oncogene Proteins c-jun/antagonists & inhibitors, Purines/pharmacology, Rats, Rats, Sprague-Dawley, Retinal Ganglion Cells/cytology, Retinal Ganglion Cells/drug effects
Pubmed
Web of science
Create date
13/01/2014 16:54
Last modification date
20/08/2019 14:23
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