Evidence that the bifunctional redox factor / AP endonuclease Ref-1 is an anti-apoptotic protein associated with differentiation in the developing retina

Cell Death Differ. 2000 Mar;7(3):272-81. doi: 10.1038/sj.cdd.4400639.


Retinal cell differentiation leads to resistance to apoptosis induced by inhibition of protein synthesis, suggesting the accumulation of anti-apoptotic proteins. The redox factor/AP endonuclease Ref-1 (APE, APEX, HAP1) affects both DNA repair and the activity of various transcription factors, and controls sensitivity to genotoxic insults. We studied the expression of Ref-1 in the retina and brain of developing rats. Ref-1 immunoreactivity increased progressively within the nucleus of differentiating retinal cells, whereas it decreased in the developing hippocampal formation. During both natural and experimentally-induced cell death, Ref-1 disappeared from the nucleus of apoptotic cells. Degradation of Ref-1 in axotomized ganglion cells preceded the morphological characteristics of apoptosis. The sensitivity to apoptosis triggered by either thapsigargin or okadaic acid was the highest in photoreceptors, that contain the least Ref-1 among differentiated retinal cells. In both these differentiated cell types, inhibition of protein synthesis prevented the loss of Ref-1 and rescued the neurons. The data suggest that Ref-1 is an anti-apoptotic protein associated with cell differentiation in the retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Brain / growth & development
  • Brain / metabolism
  • Carbon-Oxygen Lyases / metabolism*
  • Cell Differentiation
  • Cells, Cultured
  • DNA-(Apurinic or Apyrimidinic Site) Lyase*
  • Endodeoxyribonucleases / metabolism*
  • Neurons / cytology
  • Rats
  • Retina / cytology*


  • Endodeoxyribonucleases
  • Carbon-Oxygen Lyases
  • Apex1 protein, rat
  • DNA-(Apurinic or Apyrimidinic Site) Lyase