(-)-Deprenyl reduces PC12 cell apoptosis by inducing new protein synthesis.

ABSTRACT

(-)-Deprenyl, a monoamine oxidase (MAO)-B inhibitor, has been shown to increase neuronal survival and to alter protein synthesis and gene expression in astrocytic or PC12 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 neuronal survival by reducing apoptosis. (-)-Deprenyl reduced both cell death and internucleosomal DNA degradation in a concentration-dependent manner and was effective at concentrations too low to inhibit MAO (< 10(-9) M). (+)-Deprenyl did not increase PC12 cell survival, and, with the exception of pargyline, other MAO-A and MAO-B inhibitors did not alter apoptotic death. Transcriptional and translational inhibition showed that the reduction in apoptosis required the induction of new protein synthesis by (-)-deprenyl. Increased survival was induced if transcription was maintained for 4 h and translation for 6 h after (-)-deprenyl addition. The findings suggest that transcriptional induction may underlie the other MAO-independent actions of (-)-deprenyl.