title: SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling.
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.
authors: The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China.|Ophthalmology Department, Zhenjiang First People's Hospital, Zhenjiang, China.
authors: Yi-Qing
authors: YQ
authors: Gong
authors: The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China.
authors: Wei
authors: W
authors: Huang
authors: The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China.
authors: Ke-Ran
authors: KR
authors: Li
authors: Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China.
authors: Yuan-Yuan
authors: YY
authors: Liu
authors: The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China.
authors: Guo-Fan
authors: GF
authors: Cao
authors: Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China.
authors: Cong
authors: C
authors: Cao
authors: The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China.
authors: Qin
authors: Q
authors: Jiang
mesh_terms: D000085:Acetates / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009154:Mutation; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: C000614067:AKT activator SC79; D000085:Acetates; D001578:Benzopyrans; D006575:Heterocyclic Compounds, 3-Ring; C548887:MK 2206; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; SC79; UV; retinal pigment epithelium