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DNA hypermethylation-mediated downregulation of antioxidant genes contributes to the early onset of cataracts in highly myopic eyes 期刊论文

编号：

45de347c-3140-4fb9-a1c8-a79fb66f7755
作者：

Zhu, Xiangjia(竺向佳)#^[1,2,3,4]Li, Dan^[1,2,3,4];Du, Yu(杜钰)^[1,2,3,4]He, Wenwen(何雯雯)^[1,2,3,4]Lu, Yi(卢奕)*^[1,2,3,4]
语种：

English
期刊：

REDOX BIOLOGY ISSN：2213-2317 2018 年 19 卷 (179 - 189) ; OCT
收录：
关键词：

Cataract High myopia DNA methylation Oxidative stress GSTP1 TXNRD2
摘要：

High myopia is recognized as a risk factor for earlier onset of nuclear cataracts. One possible explanation for this is that lenses in highly myopic eyes are exposed to higher levels of oxygen than normal eyes owing to earlier vitreous liquefaction and, hence, are subjected to oxidative insults. Here, we first compared the methylation levels of six essential antioxidant genes (GSTP1, NRF2, OGG1, TXN, TXNRD1 and TXNRD2) between highly myopic cataract (HMC) and age-related cataract (ARC) lens epithelial samples via Sequenom MassARRAY. We found that specific CpG units in the promoters of GSTP1 and TXNRD2 were hypermethylated and that the expression levels of these two genes were lower in the HMC group than in the ARC group. A luciferase reporter assay confirmed the significance of differentially methylated fragments in the activation of transcription. The importance of GSTP1 and TXNRD2 in antioxidant capacity was confirmed by overexpression or knockdown experiments on cultured lens epithelial cells (LECs). In addition, the expression of DNA methyl transferase 1 (DNMT1) was higher in the lens epithelium of HMC patients than that of ARC patients, and the expression of GSTP1 and TXNRD2 was upregulated by use of a DNMT inhibitor in cultured LECs. Finally, we mimicked the intraocular environment of highly myopic eyes by treating LECs with hydrogen peroxide (H2O2) and observed both alterations in the methylation status of the GSTP1 and TXNRD2 promoters and time-dependent altered expression levels. Therefore, we propose that in an environment with high oxygen, in which lenses in highly myopic eyes are immersed, there exists a vicious cycle composed of increased oxidative stress and decreased enzymatic antioxidants via the hypermethylation of antioxidant genes.
推荐引用方式
GB/T 7714：

Zhu Xiangjia,Li Dan,Du Yu, et al. DNA hypermethylation-mediated downregulation of antioxidant genes contributes to the early onset of cataracts in highly myopic eyes [J].REDOX BIOLOGY,2018,19:179-189.
APA：

Zhu Xiangjia,Li Dan,Du Yu,He Wenwen,&Lu Yi.(2018).DNA hypermethylation-mediated downregulation of antioxidant genes contributes to the early onset of cataracts in highly myopic eyes .REDOX BIOLOGY,19:179-189.
MLA：

Zhu Xiangjia, et al. "DNA hypermethylation-mediated downregulation of antioxidant genes contributes to the early onset of cataracts in highly myopic eyes" .REDOX BIOLOGY 19(2018):179-189.

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