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Author Xie, Laiqing ♦ Cheng, Long ♦ Xu, Guoxu ♦ Zhang, Ji ♦ Ji, Xiaoyan ♦ Song, E.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ DEATH ♦ DNA DAMAGES ♦ EPITHELIUM ♦ GANGLIONS ♦ INHIBITION ♦ LEAD COMPOUNDS ♦ MITOCHONDRIA ♦ RADIATION INJURIES ♦ RHODOPSIN ♦ ULTRAVIOLET RADIATION
Abstract 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. - Highlights: • Compound 19 protects retinal pigment epithelium cells and retinal ganglion cells from UV. • Compound 19-mediated cytoprotection against UV requires Cyp-D. • Compound 19 shuts down UV-induced mitochondrial death pathway. • Compound 19 inhibits UV-induced ROS production, lipid peroxidation and DNA damage.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2017-06-10
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 487
Issue Number 4


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