Do c-Jun, c-Fos, and amyloid precursor protein play a role in neuronal death or survival?
A unilateral hypoxic-ischemic (HI) episode in immature rat brain was used to investigate the role of the immediate early genes c-fos and c-jun in delayed neuronal death and survival. This HI paradigm results in an apoptotic cell death in selectively vulnerable areas, in particular the hippocampal CA1 pyramidal cell layer. In susceptible regions undergoing delayed neuronal death there was a prolonged induction of both c-Jun and c-Fos (mRNA and protein). This expression occurred in parallel with a pronounced increase in AP-1 DNA binding activity but was not associated with either increased levels of Jun NH2-terminal kinase or phosphorylation of c-Jun (ser-63). In addition to changes in immediate early gene expression, the CA1 neurons showed a delayed increase in the expression of amyloid precursor protein (APP751) mRNA, suggesting that APP, which contains an AP-1 site, might be a down-stream gene regulated by the Jun transcription factor in neurons dying by apoptosis. The surviving dentate granule cells also showed an increase in Fos, Jun, and APP751 although this expression occurred earlier than in the CA1 neurons and declined rapidly. These results are discussed with respect to the role of these proteins in neuronal death and survival.
Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine and Health Science, University of Auckland, New Zealand.
M
M
Walton
G
G
MacGibbon
D
D
Young
E
E
Sirimanne
C
C
Williams
P
P
Gluckman
M
M
Dragunow
D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009474:Neurons / Q000737:chemistry / Q000166:cytology* / Q000201:enzymology; D011485:Protein Binding / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases