Activating transcription factor 3 up-regulated by c-Jun NH(2)-terminal kinase/c-Jun contributes to apoptosis induced by potassium deprivation in cerebellar granule neurons

Neuroscience. 2008 Feb 6;151(3):771-9. doi: 10.1016/j.neuroscience.2007.10.057. Epub 2007 Dec 4.


Cerebellar granule neurons (CGNs) depend on potassium depolarization for survival and undergo apoptosis when deprived of depolarizing concentration of potassium. Activating transcription factor 3 (ATF3), a stress-inducible protein, belongs to the ATF/CREB family of transcription factors family and is involved in cell growth and apoptosis. However, the role of ATF3 in neuronal apoptosis remains unknown. Here, we showed that ATF3 was up-regulated under potassium deprivation in CGNs, and this induction was preceded by a rapid and sustained activation of c-Jun NH(2)-terminal kinase/c-Jun signaling pathway, which plays a fundamental role in neuronal apoptosis. Furthermore, ATF3 up-regulation was abolished by inhibition of JNK or knockdown of c-Jun. Finally, knockdown of ATF3 by RNA interference protected CGNs from potassium deprivation-induced apoptosis. Taken together, our results indicate that ATF3 is a downstream target of JNK/c-Jun pathway and contributes to apoptosis induced by potassium deprivation in rat CGNs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 3 / genetics
  • Activating Transcription Factor 3 / metabolism*
  • Animals
  • Animals, Newborn
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Cells, Cultured
  • Cerebellum / cytology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Galactosides / genetics
  • Galactosides / metabolism
  • Green Fluorescent Proteins / metabolism
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Luciferases / metabolism
  • Neurons / drug effects
  • Neurons / physiology*
  • Potassium Chloride / pharmacology
  • Potassium Deficiency / physiopathology*
  • RNA, Small Interfering / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Transfection
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*


  • Activating Transcription Factor 3
  • Enzyme Inhibitors
  • Galactosides
  • RNA, Small Interfering
  • beta-galactoside
  • Green Fluorescent Proteins
  • Potassium Chloride
  • Luciferases
  • JNK Mitogen-Activated Protein Kinases