SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling.
SC79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling.
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SC79 通过激活 Akt-Nrf2 信号传导保护视网膜色素上皮细胞免受紫外线辐射
DOI：
10.18632/oncotarget.11164
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发表时间：
2016-09-13
期刊：
影响因子：
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通讯作者：
Jiang Q
中科院分区：
文献类型：
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作者：
Gong YQ;Huang W;Li KR;Liu YY;Cao GF;Cao C;Jiang Q
过量的紫外线（UV）辐射可引起视网膜色素上皮（RPE）细胞的氧化损伤和凋亡。在这里，我们测试了Akt的一种新型小分子激活剂SC79对这一过程的潜在活性。我们发现SC79在原代和建立的（ARPE-19系）RPE细胞中激活了Akt。它可能通过抑制细胞凋亡来保护RPE细胞免受紫外线损伤。通过Akt特异性抑制剂（MK-2206）或Akt1 shRNA沉默抑制Akt，几乎可以消除sc79诱导的RPE细胞保护作用。进一步研究表明，SC79激活akt依赖性nf - e2相关因子2 （Nrf2）信号通路，抑制紫外线诱导的RPE细胞氧化应激。相反，Nrf2 shRNA敲低或S40T突变会减弱sc79诱导的抗紫外线活性。在体内研究中，我们发现玻璃体内注射SC79可显著保护小鼠视网膜免受光损伤。基于这些结果，我们认为SC79可能通过激活Akt-Nrf2信号轴来保护RPE细胞免受紫外线损伤。
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.