Anisomycin affects both pro- and antiapoptotic mechanisms in PC12 cells

Biochem Biophys Res Commun. 2000 Nov 30;278(3):550-6. doi: 10.1006/bbrc.2000.3836.

Abstract

Survival and differentiation of PC12 cells depend on the proper balance between the activities of several mitogen-activated protein kinase (MAPK) pathways. We have previously shown that low, nontoxic doses of anisomycin stimulated these MAPKs as well as the expression of several early-response genes and inhibited NGF-induced neurite formation. In the present work we show that protein synthesis-inhibiting concentrations of anisomycin, in contrast, cause apoptosis of PC12 cells. To try to characterize the apoptosis-inducing mechanisms of anisomycin we compared the signaling effects of subinhibitory and inhibitory drug concentrations. Anisomycin in a nontoxic dosis activates the same MAPK pathways and early-response genes as in protein synthesis inhibiting concentrations. In contrast, while the subinhibitory anisomycin treatment stimulates Akt and induces Bcl-2, two antiapoptotic proteins, the translation-inhibiting concentration of the drug prevents these survival-promoting biochemical events. Anisomycin thus triggers both pro- and antiapoptotic processes in PC12 cells; stimulation of stress-responsive MAPK cascades is not sufficient to mediate apoptotic signaling: the inhibition of key antiapoptotic proteins appears to be more important for PC12 cell death by anisomycin treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anisomycin / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • DNA Fragmentation
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects*
  • Genes, Immediate-Early / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • PC12 Cells
  • Protein Biosynthesis / drug effects
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Rats

Substances

  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Anisomycin
  • Akt1 protein, rat
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases