Evidence that the bifunctional redox factor / AP endonuclease Ref-1 is an anti-apoptotic protein associated with differentiation in the developing retina.
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.
Chiarini
L B
LB
Instituto de Biofisica da UFRJ, Rio de Janeiro, Brasil.
Freitas
F G
FG
Petrs-Silva
H
H
Linden
R
R
D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D019757:Carbon-Oxygen Lyases / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D009474:Neurons / Q000166:cytology; D051381:Rats; D012160:Retina / Q000166:cytology*
D004706:Endodeoxyribonucleases; D019757:Carbon-Oxygen Lyases; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase