SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling

Oncotarget. 2016 Sep 13;7(37):60123-60132. doi: 10.18632/oncotarget.11164.

Abstract

Excessive Ultra-violet (UV) radiation causes oxidative damages and apoptosis in retinal pigment epithelium (RPE) cells. Here we tested the potential activity of SC79, a novel small molecule activator of Akt, against the process. We showed that SC79 activated Akt in primary and established (ARPE-19 line) RPE cells. It protected RPE cells from UV damages possibly via inhibiting cell apoptosis. Akt inhibition, via an Akt specific inhibitor (MK-2206) or Akt1 shRNA silence, almost abolished SC79-induced RPE cytoprotection. Further studies showed that SC79 activated Akt-dependent NF-E2-related factor 2 (Nrf2) signaling and inhibited UV-induced oxidative stress in RPE cells. Reversely, Nrf2 shRNA knockdown or S40T mutation attenuated SC79-induced anti-UV activity. For the in vivo studies, we showed that intravitreal injection of SC79 significantly protected mouse retina from light damages. Based on these results, we suggest that SC79 protects RPE cells from UV damages possibly via activating Akt-Nrf2 signaling axis.

Keywords: Akt; SC79; UV; retinal pigment epithelium.

MeSH terms

  • Acetates / chemistry
  • Acetates / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Benzopyrans / chemistry
  • Benzopyrans / pharmacology*
  • Cell Line
  • Cells, Cultured
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Molecular Structure
  • Mutation
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Oxidative Stress / radiation effects
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA Interference
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / radiation effects
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Signal Transduction / radiation effects
  • Ultraviolet Rays

Substances

  • 2-amino-6-chloro-alpha-cyano-3-(ethoxycarbonyl)-4H-1-benzopyran-4-acetic acid ethyl ester
  • Acetates
  • Benzopyrans
  • Heterocyclic Compounds, 3-Ring
  • MK 2206
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Proto-Oncogene Proteins c-akt