The novel cyclophilin D inhibitor compound 19 protects retinal pigment epithelium cells and retinal ganglion cells from UV radiation
- Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China)
- Department of Interventional Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004 (China)
- 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. - 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.
- OSTI ID:
- 22697053
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 487, Issue 4; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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