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.