学科主题 | 临床医学 |
Enhanced HtrA2/Omi Expression in Oxidative Injury to Retinal Pigment Epithelial Cells and Murine Models of Neurodegeneration | |
Ding, Xiaoyan1,2; Patel, Mrinali1,3; Shen, Defen1; Herzlich, Alexandra A.1; Cao, Xiaoguang1,4; Villasmil, Rafael; Klupsch, Kristina5; Tuo, Jingsheng1; Downward, Julian5; Chan, Chi-Chao1 | |
刊名 | INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
![]() |
2009-10-01 | |
DOI | 10.1167/iovs.09-3381 |
卷 | 50期:10页:4957-4966 |
收录类别 | SCI |
文章类型 | Article |
WOS标题词 | Science & Technology |
类目[WOS] | Ophthalmology |
资助者 | National Institutes of Health Intramural Research Foundation ; National Institutes of Health Intramural Research Foundation |
研究领域[WOS] | Ophthalmology |
关键词[WOS] | HTRA1 PROMOTER POLYMORPHISM ; SERINE-PROTEASE OMI/HTRA2 ; MACULAR DEGENERATION ; NEUROPROTECTIVE ROLE ; FAMILY PROTEINS ; APOPTOSIS ; DISEASE ; DEATH ; RPE ; MITOCHONDRIA |
英文摘要 | PURPOSE. To investigate the role of HtrA2/Omi, a nuclear-encoded mitochondrial serine protease with a proapoptosis function, under H(2)O(2)-induced oxidative stress in human RPE, in the Ccl2(-/-) Cx3cr1(-/-) double-knockout (DKO) mouse retina, and the HtrA2/Omi-deficient mice. METHODS. Oxidative stress was induced in ARPE-19 cells by 1 mM H(2)O(2) for 2 hours. HtrA2/Omi and caspase-3 expression was evaluated using RQ-PCR, immunohistochemistry, or Western blot. Cell viability was detected by MTT assay. HtrA2/Omi expression in the subcellular components and activated caspase-3 were measured. These processes were also evaluated in cells treated with UCF-101, an HtrA2/Omi inhibitor or in cells subjected to RNAi against HtrA2/Omi. Oxidative stress was assayed and compared in retinas of DKO and wild-type (WT) mice by determining serum NADPH oxidase subunits and nitrite levels. Transmission electron microscopy was used to view the retinal ultrastructure of the HtrA2/Omi-deficient mice. RESULTS. H(2)O(2)-induced oxidative damage resulted in HtrA2/Omi translocation from mitochondria to cytosol, leading to RPE cell apoptosis via a caspase-mediated pathway. Treatment of RPE cells with UCF-101 reduced the cytosolic translocation of HtrA2/Omi, attenuated caspase-3 activation, and decreased apoptosis. After specific HtrA2 downregulation, increased cell viability was measured in H(2)O(2)-treated ARPE-19 cells. Retina of DKO mice exhibit increased oxidative stress and upregulation of HtrA2/Omi. Fewer and abnormal mitochondria were found in HtrA2/Omi(-/-) photoreceptors and RPE. CONCLUSIONS. These findings suggest that HtrA2/Omi is related to RPE apoptosis due to oxidative stress, which may play an important role in the integrity of mitochondria and the pathogenesis of AMD. (Invest Ophthalmol Vis Sci. 2009; 50: 4957-4966) DOI: 10.1167/iovs.09-3381 |
语种 | 英语 |
资助者 | National Institutes of Health Intramural Research Foundation ; National Institutes of Health Intramural Research Foundation |
WOS记录号 | WOS:000270097200057 |
Citation statistics | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.bjmu.edu.cn/handle/400002259/59822 |
Collection | 北京大学第二临床医学院_眼科 |
作者单位 | 1.Howard Hughes Med Inst, Chevy Chase, MD USA 2.Canc Res UK London Res Inst, Signal Transduct Lab, London, England 3.NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA 4.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou 510275, Guangdong, Peoples R China 5.Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100871, Peoples R China |
Recommended Citation GB/T 7714 | Ding, Xiaoyan,Patel, Mrinali,Shen, Defen,et al. Enhanced HtrA2/Omi Expression in Oxidative Injury to Retinal Pigment Epithelial Cells and Murine Models of Neurodegeneration[J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,2009,50(10):4957-4966. |
APA | Ding, Xiaoyan.,Patel, Mrinali.,Shen, Defen.,Herzlich, Alexandra A..,Cao, Xiaoguang.,...&Chan, Chi-Chao.(2009).Enhanced HtrA2/Omi Expression in Oxidative Injury to Retinal Pigment Epithelial Cells and Murine Models of Neurodegeneration.INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,50(10),4957-4966. |
MLA | Ding, Xiaoyan,et al."Enhanced HtrA2/Omi Expression in Oxidative Injury to Retinal Pigment Epithelial Cells and Murine Models of Neurodegeneration".INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 50.10(2009):4957-4966. |
Files in This Item: | There are no files associated with this item. |
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment