Evidence map›Paper›PMID 39841110›Full record

ArticleInvestigative ophthalmology & visual science2025

DNA-Dependent Protein Kinase Catalytic Subunit Prevents Ferroptosis in Retinal Pigment Epithelial Cells.

Xueying Wang, Xi Wang, Zhenzhen Zhao, Qian Wang, Xiaoman Zhu, Qingjian Ou, Jing-Ying Xu, Lixia Lu, Furong Gao, Juan Wang and 4 more

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In one paragraph

Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

14 authors.

Xueying WangDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Xi WangDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Zhenzhen ZhaoDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Qian WangDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Xiaoman ZhuDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Qingjian OuDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Jing-Ying XuDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Lixia LuDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Furong GaoDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Juan WangDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Yanlong BiDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Guo-Tong XuDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Caixia JinDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.
Haibin TianDepartment of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, School of Medicine, Tongji University, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: The purpose of this study was to investigate the activated core kinases involved in the DNA damage responses (DDR) during ferroptosis of retinal pigment epithelial (RPE) cells in vitro and their regulatory effects on ferroptosis. Methods: Ferroptosis was induced by erastin in induced RPE (iRPE) cells derived from human umbilical cord mesenchymal stem cells (hUCMSCs), hUCMSCs, and induced pluripotent stem cell-derived RPE (iPSC-RPE) cells. CCK8 was employed to measure the cell viability. Calcein/PI staining was used to detect the ferroptotic cells. The γ-H2AX, 8-oxoG, and phosphorylated DNA-dependent protein kinase catalytic subunit (DNA-PKcs) were determined through immunostaining. The phosphorylation of DNA-PKcs and ERK1/2 was determined by Western blotting. Lipid peroxides were detected by BODIPY581/591-C11 staining. Results: The iRPE cells exhibited a stronger ability to resist ferroptosis compared to hUCMSCs. Ferroptosis induced DNA damage in cells, and DNA-PKcs was rapidly phosphorylated in iRPE cells on the treatment of erastin. In addition, inhibition of DNA-PKcs phosphorylation promoted ferroptosis in iRPE cells, suggesting that DNA-PKcs prevents ferroptosis. Meanwhile, DNA-PKcs inhibited ERK1/2 phosphorylation only at the early stage of ferroptosis induction, whereas ERK1/2 phosphorylation played a protective role in iRPE cells. Furthermore, erastin inducing DNA-PKcs phosphorylation and inhibition of its phosphorylation promoting ferroptosis were also verified in iPSC-RPE cells. Conclusions: The present study elucidates that the key DDR kinase DNA-PKcs is activated and plays protective role during ferroptosis in RPE cells in vitro, which will provide new research targets and strategies for inhibiting ferroptosis in RPE cells.

Indexed as

DNA-Activated Protein KinaseFerroptosisRetinal Pigment EpitheliumBlotting, WesternCells, CulturedCell SurvivalDNA DamageHumansInduced Pluripotent Stem CellsMesenchymal Stem CellsPhosphorylationPiperazinesDNA-Activated Protein KinaseerastinPiperazines

Identifiers

PMID39841110
PMCPMC11756607

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.