Survival-Promoting Activity of Inhibitors of Cyclin-Dependent Kinases on Primary Neurons Correlates with Inhibition of c-Jun Kinase-1

Cyclin-dependent kinases and mitogen-activated protein kinases have been implicated in the regulation of cellular survival and apoptosis. We tested the effect of two mitogen-activated/cyclin-dependent kinase inhibitors, olomoucine and butyrolactone I, on thein vitrosurvival of chick embryonic neuron...

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Main Authors: Marc A. Markus, Philipp J. Kahle, Andrea Winkler, Sonja Horstmann, Johanna M.H. Anneser, Gian Domenico Borasio
Format: Article
Language:English
Published: Elsevier 1997-01-01
Series:Neurobiology of Disease
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996197901406
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author Marc A. Markus
Philipp J. Kahle
Andrea Winkler
Sonja Horstmann
Johanna M.H. Anneser
Gian Domenico Borasio
author_facet Marc A. Markus
Philipp J. Kahle
Andrea Winkler
Sonja Horstmann
Johanna M.H. Anneser
Gian Domenico Borasio
author_sort Marc A. Markus
collection DOAJ
description Cyclin-dependent kinases and mitogen-activated protein kinases have been implicated in the regulation of cellular survival and apoptosis. We tested the effect of two mitogen-activated/cyclin-dependent kinase inhibitors, olomoucine and butyrolactone I, on thein vitrosurvival of chick embryonic neurons. Sensory, sympathetic, and ciliary neurons, when prepared at their respective time point of programmed cell death, could be rescued from apoptosis by both inhibitors in a dose-dependent fashion. In contrast, dividing sympathetic precursors underwent apoptosis when treated with olomoucine, but not butyrolactone I, at the same range of concentration. With similar potency, olomoucine and butyrolactone I inhibited immunocomplex c-Jun kinase activity. Both substances inhibited neurite outgrowth in a dose-dependent manner; developmentally younger neurons were more sensitive to this effect than older ones. These results suggest that certain mitogen-activated/cyclin-dependent kinases associated with cell division in neuronal precursors (i) may become essential components of the apoptotic machinery by the time neurons reach their phase of naturally occurring cell death and (ii) may be necessary for neurite outgrowth during development.
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spelling doaj.art-5663b0c5558842f08b6f1d62e09239422022-12-21T21:56:33ZengElsevierNeurobiology of Disease1095-953X1997-01-0142122133Survival-Promoting Activity of Inhibitors of Cyclin-Dependent Kinases on Primary Neurons Correlates with Inhibition of c-Jun Kinase-1Marc A. Markus0Philipp J. Kahle1Andrea Winkler2Sonja Horstmann3Johanna M.H. Anneser4Gian Domenico Borasio5Department of Neurology, Ludwig-Maximilians-University, Klinikum Grosshadern, D-81366, Munich, Germany; Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305-5401Department of Neurology, Ludwig-Maximilians-University, Klinikum Grosshadern, D-81366, Munich, Germany; Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305-5401Department of Neurology, Ludwig-Maximilians-University, Klinikum Grosshadern, D-81366, Munich, Germany; Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305-5401Department of Neurology, Ludwig-Maximilians-University, Klinikum Grosshadern, D-81366, Munich, Germany; Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305-5401Department of Neurology, Ludwig-Maximilians-University, Klinikum Grosshadern, D-81366, Munich, Germany; Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305-5401Department of Neurology, Ludwig-Maximilians-University, Klinikum Grosshadern, D-81366, Munich, Germany; Department of Neurobiology, Stanford University School of Medicine, Stanford, California, 94305-5401Cyclin-dependent kinases and mitogen-activated protein kinases have been implicated in the regulation of cellular survival and apoptosis. We tested the effect of two mitogen-activated/cyclin-dependent kinase inhibitors, olomoucine and butyrolactone I, on thein vitrosurvival of chick embryonic neurons. Sensory, sympathetic, and ciliary neurons, when prepared at their respective time point of programmed cell death, could be rescued from apoptosis by both inhibitors in a dose-dependent fashion. In contrast, dividing sympathetic precursors underwent apoptosis when treated with olomoucine, but not butyrolactone I, at the same range of concentration. With similar potency, olomoucine and butyrolactone I inhibited immunocomplex c-Jun kinase activity. Both substances inhibited neurite outgrowth in a dose-dependent manner; developmentally younger neurons were more sensitive to this effect than older ones. These results suggest that certain mitogen-activated/cyclin-dependent kinases associated with cell division in neuronal precursors (i) may become essential components of the apoptotic machinery by the time neurons reach their phase of naturally occurring cell death and (ii) may be necessary for neurite outgrowth during development.http://www.sciencedirect.com/science/article/pii/S0969996197901406
spellingShingle Marc A. Markus
Philipp J. Kahle
Andrea Winkler
Sonja Horstmann
Johanna M.H. Anneser
Gian Domenico Borasio
Survival-Promoting Activity of Inhibitors of Cyclin-Dependent Kinases on Primary Neurons Correlates with Inhibition of c-Jun Kinase-1
Neurobiology of Disease
title Survival-Promoting Activity of Inhibitors of Cyclin-Dependent Kinases on Primary Neurons Correlates with Inhibition of c-Jun Kinase-1
title_full Survival-Promoting Activity of Inhibitors of Cyclin-Dependent Kinases on Primary Neurons Correlates with Inhibition of c-Jun Kinase-1
title_fullStr Survival-Promoting Activity of Inhibitors of Cyclin-Dependent Kinases on Primary Neurons Correlates with Inhibition of c-Jun Kinase-1
title_full_unstemmed Survival-Promoting Activity of Inhibitors of Cyclin-Dependent Kinases on Primary Neurons Correlates with Inhibition of c-Jun Kinase-1
title_short Survival-Promoting Activity of Inhibitors of Cyclin-Dependent Kinases on Primary Neurons Correlates with Inhibition of c-Jun Kinase-1
title_sort survival promoting activity of inhibitors of cyclin dependent kinases on primary neurons correlates with inhibition of c jun kinase 1
url http://www.sciencedirect.com/science/article/pii/S0969996197901406
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