Apoptosis of cerebellar granule cells induced by serum withdrawal, glutamate or beta-amyloid, is independent of Jun kinase or p38 mitogen activated protein kinase activation.
It has been reported that in differentiated PC12 cells and neurons from the superior cervical ganglion and hippocampus, that the activation of the stress-activated protein kinases jun-N-terminal kinase (JNK) and/or p38 mitogen-activated protein (p38MAP) kinase is central to the induction of apoptosis by serum or neurotrophic factor withdrawal. Here we demonstrate that in cerebellar granule cells, withdrawal of serum does not result in the activation of JNK or p38MAP kinase, under conditions where profound apoptosis was observed. In addition, these protein kinases were not activated during the induction of apoptosis caused by addition of excitotoxic levels of glutamate or of beta-amyloid (25-35) peptide. BDNF and insulin can prevent apoptosis induced by serum withdrawal or the addition of glutamate or beta-amyloid peptide. EGF on the other can prevent apoptosis induced by glutamate and beta-amyloid peptide, but not that caused by serum withdrawal. We conclude that the induction of apoptosis of cerebellar granule cells is independent of JNK or p38MAP kinase activation and that the mechanism by which serum withdrawal promotes apoptosis of these neurons may differ from that caused by glutamate and beta-amyloid peptide.
Gunn-Moore
F J
FJ
Department of Biochemistry, School of Medical Sciences, University of Bristol, UK. f.j.gunn-moore@bristol.ac.uk
Tavaré
J M
JM
D016229:Amyloid beta-Peptides / Q000097:blood* / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D004789:Enzyme Activation; D018698:Glutamic Acid / Q000097:blood* / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009474:Neurons / Q000166:cytology / Q000502:physiology; D016716:PC12 Cells / Q000166:cytology / Q000502:physiology; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases
D016229:Amyloid beta-Peptides; D018698:Glutamic Acid; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases