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The effects of quercetin in cultured human RPE cells under oxidative stress and in Ccl2/Cx3cr1 double deficient mice
Cao, Xiaoguang1,2; Liu, Melissa1; Tuo, Jingsheng1; Shen, Defen1; Chan, Chi-Chao1
关键词Quercetin Rpe Age-related Macular Degeneration Oxidative Stress Inflammation Apoptosis Amd Mouse Model
刊名EXPERIMENTAL EYE RESEARCH
2010-07-01
DOI10.1016/j.exer.2010.03.016
91期:1页:15-25
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Ophthalmology
研究领域[WOS]Ophthalmology
关键词[WOS]RETINAL-PIGMENT EPITHELIUM ; MITOCHONDRIAL-DNA DAMAGE ; MACULAR DEGENERATION ; HYDROGEN-PEROXIDE ; IN-VITRO ; LUNG INFLAMMATION ; ACID HYDROPEROXIDE ; LIPID-PEROXIDATION ; GENE-EXPRESSION ; OUTER SEGMENTS
英文摘要

Quercetin, a member of the flavonoid family, is one of the most prominent dietary antioxidants. This study investigates the mechanisms for the effects of quercetin on cultured human RPE cells and in Ccl2/Cx3cr1 double knock-out (DKO) mice, which spontaneously develop progressive retinal lesions mimicking age-related macular degeneration (AMD). In the in vitro experiment, cultured ARPE-19 cells were exposed to 1 mM H(2)O(2) with or without 50 mu M quercetin for 2 h. Cellular viability, mitochondrial function, and apoptosis were assessed using crystal violet staining, MTT assay, and comet assay, respectively. Apoptotic molecular transcripts of BCL-2, BAX, MUD, CASPASE-3 and CASPASE-9 were measured by RQ-PCR. COX activity and nitric oxide (NO) level were determined in the supernatant of the culture medium. Quercetin treatment protected ARPE-19 cells from H(2)O(2)-induced oxidative injury, enhanced BCL-2 transcript levels, increased the BCL-2/BAX ratio, suppressed the transcription of proapoptotic factors such as BAX, FADD, CASPASE-3 and CASPASE-9, inhibited the transcription of inflammatory factors such as TNF-alpha, COX-2 and INOS, and decreased the levels of COX and NO in the culture medium. In the in vivo experiment, DKO and C57/B6 mice were treated with 25 mg/kg/day quercetin by intraperitoneal injection daily for two months. Funduscopy was performed monthly. After two months, serum was collected to measure NADP(+)/NADPH, COX, PGE-2, and NO levels. The eyes were harvested for histology and A2E measurement. Ocular transcripts of Bcl-2, Bax, Cox-2, Inos, Tnf-alpha, Fas, Fast and Caspase-3 were detected by RQ-PCR. Quercetin treatment did not reverse the progression of retinal lesions in DKO mice funduscopically or histologically. Although quercetin treatment could recover systemic anti-oxidative capacity, suppress the systemic expression of NO, COX and PGE-2, and decrease ocular A2E levels, it could not effectively suppress the transcripts of the ocular inflammatory factors Trif-a, Cox-2 and Inos, or the pro-apoptotic factors Fas, FasL and Caspase-3 in DKO mice. Our data demonstrate that quercetin can protect human RPE cells from oxidative stress in vitro via inhibition of pro-inflammatory molecules and direct inhibition of the intrinsic apoptosis pathway. However, quercetin (25 mg/kg/day) does not improve the retinal AMD-like lesions in the Ccl2(-/-)/Cx3cr1(-/-) mice, likely due to its insufficient suppression of the inflammatory and apoptosis pathways in the eye. Published by Elsevier Ltd.

语种英语
WOS记录号WOS:000278804700003
资助机构National Eye Institute, NIH
引用统计
被引频次:30[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53734
专题北京大学第二临床医学院_眼科
作者单位1.NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA
2.Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100044, Peoples R China
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GB/T 7714
Cao, Xiaoguang,Liu, Melissa,Tuo, Jingsheng,et al. The effects of quercetin in cultured human RPE cells under oxidative stress and in Ccl2/Cx3cr1 double deficient mice[J]. EXPERIMENTAL EYE RESEARCH,2010,91(1):15-25.
APA Cao, Xiaoguang,Liu, Melissa,Tuo, Jingsheng,Shen, Defen,&Chan, Chi-Chao.(2010).The effects of quercetin in cultured human RPE cells under oxidative stress and in Ccl2/Cx3cr1 double deficient mice.EXPERIMENTAL EYE RESEARCH,91(1),15-25.
MLA Cao, Xiaoguang,et al."The effects of quercetin in cultured human RPE cells under oxidative stress and in Ccl2/Cx3cr1 double deficient mice".EXPERIMENTAL EYE RESEARCH 91.1(2010):15-25.
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