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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
DOI10.1167/iovs.09-3381
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
Cited Times:21[WOS]   [WOS Record]     [Related Records in WOS]
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.
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