ARNT2, a transcription factor for brain neuron survival?

Eur J Neurosci. 1999 May;11(5):1545-53. doi: 10.1046/j.1460-9568.1999.00562.x.


The processes responsible for the limited ability to divide and long survival of neurons are not well understood but may involve aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), a recently identified protein, apparently belonging to the basic helix-loop-helix superfamily of transcription factors, which is expressed almost exclusively in brain during the whole lifetime. In agreement, we show, in the rat, that ARNT2 immunoreactivity could be observed only within nuclei of brain neurons and of dividing and neuronal PC12 cells, a localization consistent with a role in transcription regulation. Cell death elicited either by focal ischaemia in brain or oxidative stress in PC12 cells was largely preceded by an almost complete suppression of ARNT2 expression. In contrast, when PC12 cell cycle progression was impaired, ARNT2 expression was enhanced. Finally, the downregulation of ARNT2 levels induced by antisense oligonucleotides prevented PC12 cell proliferation and induced apoptosis. These observations support the hypothesis that ARNT2 is a neuronal transcription factor, regulating cell cycle progression and preventing cell death, whose sustained expression might ensure brain neuron survival.

MeSH terms

  • Age Factors
  • Animals
  • Antisense Elements (Genetics)
  • Apoptosis / physiology
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Basic Helix-Loop-Helix Transcription Factors
  • Brain Ischemia / genetics
  • Brain Ischemia / physiopathology
  • Cell Cycle / physiology
  • Cell Survival / physiology
  • Cerebral Cortex / blood supply
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Down-Regulation / physiology
  • Gene Expression Regulation, Developmental / physiology
  • In Situ Nick-End Labeling
  • Male
  • Neurons / chemistry*
  • Neurons / cytology*
  • Neurons / physiology
  • PC12 Cells
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Antisense Elements (Genetics)
  • Arnt2 protein, rat
  • Basic Helix-Loop-Helix Transcription Factors
  • RNA, Messenger
  • Transcription Factors
  • Aryl Hydrocarbon Receptor Nuclear Translocator