Changes in gene transcription during a beta-mediated cell death.
The a beta peptide induces cell death in neurons grown in cell culture. Previous studies have shown that the mechanism of a beta-mediated cell death of central nervous system neurons appears to be via apoptosis. Apoptosis is an active process that involves both gene transcription and translation. Using semi-quantitative polymerase chain reaction, we have analyzed the levels of a variety of transcripts in primary neuronal cultures treated with a beta that are likely to play important roles in apoptosis. Following addition of 10 microM a beta 1-42 the immediate early response gene, c-fos, shows a rapid and sustained increase in transcript level while c-jun levels increase at a slower rate. Bcl-2 and its homologues, bcl-X and bax, also increase in amount with bcl-2 and bcl-X increasing more rapidly than bax. These data provide support indicating that a beta-mediated cell death in central nervous system neurons is an active process similar to that seen in apoptosis.
Iwasaki
K
K
Section on Geriatric Psychiatry, National Institute of Mental Health, Bethesda, MD 20892-1264, USA.
Sunderland
T
T
Kusiak
J W
JW
Wolozin
B
B
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole; D002453:Cell Cycle / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D002540:Cerebral Cortex / Q000166:cytology; D053938:DNA Fragmentation; D015342:DNA Probes; D004259:DNA-Directed DNA Polymerase; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D042843:Glucose 1-Dehydrogenase; D005948:Glucose Dehydrogenases / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014158:Transcription, Genetic / Q000502:physiology*
D016229:Amyloid beta-Peptides; D015342:DNA Probes; D019253:Proto-Oncogene Proteins c-bcl-2; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D005948:Glucose Dehydrogenases; D042843:Glucose 1-Dehydrogenase; C034970:bacteriophage T7 induced DNA polymerase; D004259:DNA-Directed DNA Polymerase; D006690:Bisbenzimidazole