PMID- 35693421 OWN - NLM STAT- MEDLINE DCOM- 20220614 LR - 20220716 IS - 1090-0535 (Electronic) IS - 1090-0535 (Linking) VI - 28 DP - 2022 TI - Protective effect of Glutaredoxin 1 against oxidative stress in lens epithelial cells of age-related nuclear cataracts. PG - 70-82 AB - PURPOSE: Glutaredoxin 1 (Grx1) is a key antioxidant protein that catalyzes disulfide redox reactions. In this study, we investigated the expression and protective effect of Grx1 against oxidative stress in nuclear cataracts. METHODS: Human anterior capsule membrane samples were obtained from the eyes of cataract patients (experimental group) and non-cataractous (control group) donors. The levels of Grx1 protein and mRNA expression were investigated. The human lens epithelial (HLE) cell line SRA 01/04 was transfected with Grx1-containing plasmid or Grx1 small interfering RNA, and cultured under H(2)O(2) treatment, mimicking oxidative stress conditions. Cell counts, clone formation, cell apoptosis, cell cycle, and levels of oxidized glutathione disulfide and cellular reactive oxygen species (ROS) were evaluated and quantified. RESULTS: Protein and mRNA transcript levels of Grx1 were significantly lower in the human anterior capsule membrane of the age-related nuclear (ARN) cataract group than in the control group. Grx1 overexpression protected HLE cells from H(2)O(2)-induced oxidative damage, including alleviating G1 phase arrest, promoting cell proliferation, reducing cell apoptosis, and decreasing intracellular ROS generation. Furthermore, extracellular-signal-regulated kinase (ERK) phosphorylation in the human anterior capsule membrane of ARN patients was higher in the experimental group than in the control group. Grx1 overexpression reduced the levels of oxidized glutathione disulfide and the phosphorylation of ERK. The administration of an ERK phosphorylation inhibitor, PD98059, induced antioxidant effects in Grx1-silenced cells. CONCLUSIONS: Grx1 expression is downregulated in the human anterior capsule membrane of ARN patients, accompanied by an increase in ERK phosphorylation. Thus, Grx1 can protect HLE cells against oxidative stress. CI - Copyright (c) 2022 Molecular Vision. FAU - Fan, Qi AU - Fan Q AD - Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China. AD - NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. AD - Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China. AD - Shanghai Research Center of Ophthalmology and Optometry, Shanghai, China. FAU - Li, Dan AU - Li D AD - Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China. AD - NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. AD - Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China. AD - Shanghai Research Center of Ophthalmology and Optometry, Shanghai, China. FAU - Zhao, Zhennan AU - Zhao Z AD - Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China. AD - NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. AD - Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China. AD - Shanghai Research Center of Ophthalmology and Optometry, Shanghai, China. FAU - Jiang, Yongxiang AU - Jiang Y AD - Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China. AD - NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. AD - Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China. AD - Shanghai Research Center of Ophthalmology and Optometry, Shanghai, China. FAU - Lu, Yi AU - Lu Y AD - Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China. AD - NHC Key Laboratory of Myopia (Fudan University); Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China. AD - Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China. AD - Shanghai Research Center of Ophthalmology and Optometry, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220519 PL - United States TA - Mol Vis JT - Molecular vision JID - 9605351 RN - 0 (Antioxidants) RN - 0 (Glutaredoxins) RN - 0 (RNA, Messenger) RN - 0 (Reactive Oxygen Species) RN - BBX060AN9V (Hydrogen Peroxide) RN - ULW86O013H (Glutathione Disulfide) SB - IM MH - Antioxidants/pharmacology MH - Apoptosis MH - *Cataract/genetics/metabolism MH - Epithelial Cells/metabolism MH - Glutaredoxins/genetics/metabolism MH - Glutathione Disulfide/metabolism/pharmacology MH - Humans MH - Hydrogen Peroxide/pharmacology MH - *Lens, Crystalline/metabolism MH - Oxidative Stress MH - RNA, Messenger/metabolism MH - Reactive Oxygen Species/metabolism PMC - PMC9122476 EDAT- 2022/06/14 06:00 MHDA- 2022/06/15 06:00 PMCR- 2022/01/01 CRDT- 2022/06/13 03:15 PHST- 2021/03/21 00:00 [received] PHST- 2022/05/17 00:00 [accepted] PHST- 2022/06/13 03:15 [entrez] PHST- 2022/06/14 06:00 [pubmed] PHST- 2022/06/15 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 8 [pii] PST - epublish SO - Mol Vis. 2022 May 19;28:70-82. eCollection 2022.