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

J Neurochem. 1994 Oct;63(4):1572-5. doi: 10.1046/j.1471-4159.1994.63041572.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • Culture Media, Serum-Free
  • DNA, Neoplasm / drug effects
  • Kinetics
  • Neoplasm Proteins / biosynthesis*
  • Nerve Growth Factors / pharmacology
  • PC12 Cells
  • Pargyline / pharmacology
  • Rats
  • Selegiline / pharmacology*
  • Time Factors

Substances

  • Culture Media, Serum-Free
  • DNA, Neoplasm
  • Neoplasm Proteins
  • Nerve Growth Factors
  • Selegiline
  • Pargyline