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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Elsevier
1997-01-01
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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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