(-)-DEPRENYL REDUCES PC12 CELL APOPTOSIS BY INDUCING NEW-PROTEIN SYNTHESIS

(-)-Deprenyl, a monoamine oxidase (MAO)-B inhibitor, has been shown to increase neuronal survival and to alter protein synthesis and gene ex pression in astrocytic or PG12 cells independently of MAO-B inhibition . We used serum and nerve growth factor withdrawal to induce apoptotic death in PC12 cells to determine whether (-)-deprenyl increases neuro nal survival by reducing apoptosis. (-)-Deprenyl reduced both cell dea th and internucleosomal DNA degradation in a concentration-dependent m anner and was effective at concentrations too low to inhibit MAO (< 10 (-9) M). (+)-Deprenyl did not increase PC12 cell survival, and, with t he exception of pargyline, other MAO-A and MAO-B inhibitors did not al ter apoptotic death. Transcriptional and translational inhibition show ed that the reduction in apoptosis required the induction of new prote in synthesis by (-)-deprenyl. Increased survival was induced a transcr iption was maintained for 4 h and translation for 6 h after (-)-depren yl addition. The findings suggest that transcriptional induction may u nderlie the other MAO-independent actions of (-)-deprenyl.