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IR@PKUHSC  > 北京大学第二临床医学院  > 眼科  > 期刊论文
学科主题: 临床医学
题名:
The effects of quercetin in cultured human RPE cells under oxidative stress and in Ccl2/Cx3cr1 double deficient mice
作者: 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
发表日期: 2010-07-01
DOI: 10.1016/j.exer.2010.03.016
卷: 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
项目资助者: National Eye Institute, NIH
WOS记录号: WOS:000278804700003
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53734
Appears in Collections:北京大学第二临床医学院_眼科_期刊论文

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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

Recommended Citation:
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.
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