WRN inhibits oxidative stress-induced apoptosis of human lensepithelial cells through ATM/p53 signaling pathway and its expression is downregulated by DNA methylation
Abstract Background Apoptosis and oxidative stress are the main etiology of age related cataract (ARC). This article aims to investigate the role of WRN in lens epithelial cells (LECs). Methods We estimated the methylation level of WRN in anterior lens capsule tissues of ARC patients. SRA01/04 (LECs...
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| Format: | Article |
| Language: | English |
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BMC
2020-07-01
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| Series: | Molecular Medicine |
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| Online Access: | http://link.springer.com/article/10.1186/s10020-020-00187-x |
| _version_ | 1818772793620168704 |
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| author | Shengqun Jiang Jiansu Chen |
| author_facet | Shengqun Jiang Jiansu Chen |
| author_sort | Shengqun Jiang |
| collection | DOAJ |
| description | Abstract Background Apoptosis and oxidative stress are the main etiology of age related cataract (ARC). This article aims to investigate the role of WRN in lens epithelial cells (LECs). Methods We estimated the methylation level of WRN in anterior lens capsule tissues of ARC patients. SRA01/04 (LECs) cells were treated with H2O2 or combined with 5-aza-2-deoxycytidine (5-Aza-CdR) or chloroquine. CCK8 and flow cytometry were performed to explore proliferation and apoptosis. The content of ROS was detected by fluorescent probe DCFH-DA. The gene and protein expression was assessed by quantitative real-time PCR or western blot. Results WRN was down-regulated and the methylation level of WRN was increased in the anterior lens capsule tissues. WRN overexpression and 5-Aza-CdR enhanced proliferation and repressed apoptosis and oxidative stress of SRA01/04 cells. 5-Aza-CdR enhanced WRN expression. WRN knockdown inhibited proliferation and promoted apoptosis and oxidative stress of SRA01/04 cells, which was rescued by 5-Aza-CdR. WRN overexpression and 5-Aza-CdR repressed ATM/p53 signaling pathway. Furthermore, chloroquine inhibited proliferation and promoted apoptosis and oxidative stress of SRA01/04 cells by activating ATM/p53 signaling pathway. The influence conferred by chloroquine was abolished by WRN overexpression. Conclusion Our study reveals that DNA methylation mediated WRN inhibits apoptosis and oxidative stress of human LECs through ATM/p53 signaling pathway. |
| first_indexed | 2024-12-18T10:15:00Z |
| format | Article |
| id | doaj.art-5d9626a3d8ac4ae3b7b88b687bf59f6a |
| institution | Directory Open Access Journal |
| issn | 1076-1551 1528-3658 |
| language | English |
| last_indexed | 2024-12-18T10:15:00Z |
| publishDate | 2020-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-5d9626a3d8ac4ae3b7b88b687bf59f6a2022-12-21T21:11:20ZengBMCMolecular Medicine1076-15511528-36582020-07-0126111210.1186/s10020-020-00187-xWRN inhibits oxidative stress-induced apoptosis of human lensepithelial cells through ATM/p53 signaling pathway and its expression is downregulated by DNA methylationShengqun Jiang0Jiansu Chen1Ophthalmology Department, The First Affiliated Hospital of Jinan University GuangzhouOphthalmology Department, The First Affiliated Hospital of Jinan University GuangzhouAbstract Background Apoptosis and oxidative stress are the main etiology of age related cataract (ARC). This article aims to investigate the role of WRN in lens epithelial cells (LECs). Methods We estimated the methylation level of WRN in anterior lens capsule tissues of ARC patients. SRA01/04 (LECs) cells were treated with H2O2 or combined with 5-aza-2-deoxycytidine (5-Aza-CdR) or chloroquine. CCK8 and flow cytometry were performed to explore proliferation and apoptosis. The content of ROS was detected by fluorescent probe DCFH-DA. The gene and protein expression was assessed by quantitative real-time PCR or western blot. Results WRN was down-regulated and the methylation level of WRN was increased in the anterior lens capsule tissues. WRN overexpression and 5-Aza-CdR enhanced proliferation and repressed apoptosis and oxidative stress of SRA01/04 cells. 5-Aza-CdR enhanced WRN expression. WRN knockdown inhibited proliferation and promoted apoptosis and oxidative stress of SRA01/04 cells, which was rescued by 5-Aza-CdR. WRN overexpression and 5-Aza-CdR repressed ATM/p53 signaling pathway. Furthermore, chloroquine inhibited proliferation and promoted apoptosis and oxidative stress of SRA01/04 cells by activating ATM/p53 signaling pathway. The influence conferred by chloroquine was abolished by WRN overexpression. Conclusion Our study reveals that DNA methylation mediated WRN inhibits apoptosis and oxidative stress of human LECs through ATM/p53 signaling pathway.http://link.springer.com/article/10.1186/s10020-020-00187-xWRNDNA methylationApoptosisOxidative stressATM/p53Age related cataract |
| spellingShingle | Shengqun Jiang Jiansu Chen WRN inhibits oxidative stress-induced apoptosis of human lensepithelial cells through ATM/p53 signaling pathway and its expression is downregulated by DNA methylation Molecular Medicine WRN DNA methylation Apoptosis Oxidative stress ATM/p53 Age related cataract |
| title | WRN inhibits oxidative stress-induced apoptosis of human lensepithelial cells through ATM/p53 signaling pathway and its expression is downregulated by DNA methylation |
| title_full | WRN inhibits oxidative stress-induced apoptosis of human lensepithelial cells through ATM/p53 signaling pathway and its expression is downregulated by DNA methylation |
| title_fullStr | WRN inhibits oxidative stress-induced apoptosis of human lensepithelial cells through ATM/p53 signaling pathway and its expression is downregulated by DNA methylation |
| title_full_unstemmed | WRN inhibits oxidative stress-induced apoptosis of human lensepithelial cells through ATM/p53 signaling pathway and its expression is downregulated by DNA methylation |
| title_short | WRN inhibits oxidative stress-induced apoptosis of human lensepithelial cells through ATM/p53 signaling pathway and its expression is downregulated by DNA methylation |
| title_sort | wrn inhibits oxidative stress induced apoptosis of human lensepithelial cells through atm p53 signaling pathway and its expression is downregulated by dna methylation |
| topic | WRN DNA methylation Apoptosis Oxidative stress ATM/p53 Age related cataract |
| url | http://link.springer.com/article/10.1186/s10020-020-00187-x |
| work_keys_str_mv | AT shengqunjiang wrninhibitsoxidativestressinducedapoptosisofhumanlensepithelialcellsthroughatmp53signalingpathwayanditsexpressionisdownregulatedbydnamethylation AT jiansuchen wrninhibitsoxidativestressinducedapoptosisofhumanlensepithelialcellsthroughatmp53signalingpathwayanditsexpressionisdownregulatedbydnamethylation |