Differential induction of immediate early gene proteins in cultured neurons by beta-amyloid (A beta): association of c-Jun with A beta-induced apoptosis.
beta-Amyloid (A beta) is a 39-42 amino acid that is the primary component of plaques in Alzheimer's disease (AD). Previous studies from our laboratory and others have shown that A beta induces neurodegeneration via apoptosis in vitro, suggesting that A beta may also initiate an apoptotic pathway of cell death in AD. Apoptosis has been suggested to proceed by a gene-directed program in several systems. Accordingly, we have investigated whether A beta-mediated apoptosis is associated with the induction of genes that may regulate or play a role in cell death in vitro. Immediate early genes (IEGs) respond to cellular stimuli and participate in cellular signaling pathways. The protein products of some IEGs, e.g., c-jun, are capable of forming dimers and acting as transcriptional regulatory proteins, and have been implicated in apoptosis in both nonneuronal and neuronal cells. In this study, we report a selective and abnormally sustained induction of c-Jun in cultured hippocampal neurons treated with A beta. In addition, we describe the lack of induction of c-Jun in neurons that are relatively resistant to A beta-mediated toxicity, and a correspondence between immunoreactivity for c-Jun and changes in nuclear morphology that are indicative of apoptosis. These data demonstrate that c-Jun is induced in cultured neurons that undergo A beta-mediated apoptosis and suggest that c-Jun may participate in a cell death program in these neurons.
Anderson
A J
AJ
Irvine Research Unit in Brain Aging, Department of Psychobiology, University of California 92717-4550, USA.
Pike
C J
CJ
Cotman
C W
CW
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D006690:Bisbenzimidazole; D002478:Cells, Cultured; D004396:Coloring Agents; D005786:Gene Expression Regulation / Q000187:drug effects*; D017781:Genes, Immediate-Early; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D015345:Oligonucleotide Probes / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D015345:Oligonucleotide Probes; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D006690:Bisbenzimidazole