(-)-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 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.
Tatton
W G
WG
Centre for Research in Neurodegenerative Diseases, University of Toronto, Ontario, Canada.
Ju
W Y
WY
Holland
D P
DP
Tai
C
C
Kwan
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004273:DNA, Neoplasm / Q000187:drug effects; D007700:Kinetics; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009414:Nerve Growth Factors / Q000494:pharmacology; D016716:PC12 Cells; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D012642:Selegiline / Q000494:pharmacology*; D013997:Time Factors
D016895:Culture Media, Serum-Free; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D012642:Selegiline; D010293:Pargyline