Brca1 Is Upregulated by 5-Aza-CdR and Promotes DNA Repair and Cell Survival, and Inhibits Neurite Outgrowth in Rat Retinal Neurons

Int J Mol Sci. 2018 Apr 17;19(4):1214. doi: 10.3390/ijms19041214.

Abstract

Previous studies have reported that Brca1 acts as a “hinge” in the development of the central nervous system (CNS). However, the precise role of Brca1 in rat retinal neurons remains unclear. Here, we found that Brca1 is developmentally downregulated and silenced in adult retina. Brca1 was upregulated in rat primary retinal neurons by 5-Aza-2′-deoxycytidine (5-Aza-CdR) treatment. Moreover, the upregulation of Brca1 by both 5-Aza-CdR and transgenic Brca1 promoted genomic stability and improved cell viability following exposure to ionizing radiation (IR). Furthermore, transgenic Brca1 significantly inhibited neurite outgrowth of retinal neurons, which implicates that Brca1 silencing promotes cell differentiation and determines neuronal morphology. Taken together, our results reveal a biological function of Brca1 in retinal development.

Keywords: 5-Aza-CdR; Brca1; neurite outgrowth; retina.

MeSH terms

  • Animals
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • BRCA1 Protein / genetics*
  • Cell Survival / drug effects
  • Cells, Cultured
  • DNA Repair / drug effects*
  • Decitabine
  • Enzyme Inhibitors / pharmacology*
  • Neuronal Outgrowth / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Neurons / cytology
  • Retinal Neurons / drug effects*
  • Retinal Neurons / metabolism
  • Up-Regulation / drug effects*

Substances

  • BRCA1 Protein
  • Enzyme Inhibitors
  • Decitabine
  • Azacitidine