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The novel cyclophilin D inhibitor compound 19 protects retinal pigment epithelium cells and retinal ganglion cells from UV radiation

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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
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关键词: Ultra violet (UV) Retinal degeneration Compound 19 p53 Cyclophilin D

摘要:
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.

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出版当年[2016]版:
大类 | 3 区 生物
小类 | 4 区 生化与分子生物学 4 区 生物物理
最新[2025]版:
大类 | 4 区 生物学
小类 | 4 区 生化与分子生物学 4 区 生物物理
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出版当年[2015]版:
Q2 BIOPHYSICS Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2024]版:
Q3 BIOPHYSICS Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

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第一作者机构: [a]Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
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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.
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