Inducible transcription factor expression in a cell culture model of apoptosis

We have developed a model of nerve cell death based on the toxicity of okad aic acid, a compound that triggers apoptosis in PC12 cells via a protein sy nthesis-dependent mechanism. The cell death process is accompanied by induc tion of JunB, c-Jun, JunD and Fos proteins. Phosphorylation-specific antibo dies were used to demonstrate that c-Jun is phosphorylated at serine 63 and serine 73. Electrophoretic gel mobility shift and pAP1-Luc luciferase assa ys showed that expression of ITFs is associated with increases in AP-1 bind ing and in AP-1 transcriptional activity. In addition, dose response and ti me course studies provided strong correlative evidence that Fos and Jun pro teins are involved in the apoptotic death cascades. Thus, this model provid es a useful system to investigate the role of inducible transcription facto r proteins in apoptosis. (C) 1999 Published by Elsevier Science B.V. All ri ghts reserved.