机构:[a]Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China[b]Department of Interventional Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China[c]Department of Ophthalmology, The First Hospital of Jilin University, Changchun 130021, China[d]Lixiang Eye Hospital of Soochow University, Suzhou, 215021, China
Excessive Ultra violet (UV) radiation induces injuries to retinal pigment epithelium (RPE) cells (RPEs) and retinal ganglion cells (RGCs), causing retinal degeneration. Cyclophilin D (Cyp-D)-dependent mitochondrial permeability transition pore (mPTP) opening mediates UV-induced cell death. In this study, we show that a novel Cyp-D inhibitor compound 19 efficiently protected RPEs and RGCs from UV radiation. Compound 19-mediated cytoprotection requires Cyp-D, as it failed to further protect RPEs/RGCs from UV when Cyp-D was silenced by targeted shRNAs. Compound 19 almost blocked UV-induced p53-Cyp-D mitochondrial association, mPTP opening and subsequent cytochrome C release. Further studies showed that compound 19 inhibited UV-induced reactive oxygen species (ROS) production, lipid peroxidation and DNA damage. Together, compound 19 protects RPEs and RGCs from UV radiation, possibly via silencing Cyp-D-regulated intrinsic mitochondrial death pathway. Compound 19 could a lead compound for treating UV-associated retinal degeneration diseases. (C) 2017 Elsevier Inc. All rights reserved.
基金:
Suzhou Science and Technology Fund of China [SS201426]; Health Leading Talent Foundation of Suzhou [025]
第一作者机构:[a]Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
共同第一作者:
通讯作者:
通讯机构:[*1]Lixiang Eye Hospital of Soochow University, The Second Affiliated Hospital of Soochow University, The First Hospital of Jilin University, Ganjiang East Road 200, Suzhou, 215021, China.
推荐引用方式(GB/T 7714):
Laiqing Xie,Long Cheng,Guoxu Xu,et al.The novel cyclophilin D inhibitor compound 19 protects retinal pigment epithelium cells and retinal ganglion cells from UV radiation[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2017,487(4):807-812.doi:10.1016/j.bbrc.2017.04.128.
APA:
Laiqing Xie,Long Cheng,Guoxu Xu,Ji Zhang,Xiaoyan Ji&E Song.(2017).The novel cyclophilin D inhibitor compound 19 protects retinal pigment epithelium cells and retinal ganglion cells from UV radiation.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,487,(4)
MLA:
Laiqing Xie,et al."The novel cyclophilin D inhibitor compound 19 protects retinal pigment epithelium cells and retinal ganglion cells from UV radiation".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 487..4(2017):807-812