論文 - 詳細
| RRC ID | 65830 |
|---|---|
| 著者 | Zheng X, Cui H, Yin Y, Zhang Y, Zong R, Bao X, Ma JX, Liu Z, Zhou Y. |
| タイトル | SERPINA3K Ameliorates the Corneal Oxidative Injury Induced by 4-Hydroxynonenal. |
| ジャーナル | Invest Ophthalmol Vis Sci |
| Abstract |
Purpose:We previously demonstrated that SERPINA3K has anti-inflammatory, antiangiogenic, and antioxidant effects in corneas. Here we further investigated the effects of SERPINA3K on the corneal oxidant injury setting recently developed and induced by 4-hydroxynonenal (4-HNE). Methods:We applied the 4-HNE-induced corneal oxidant stress in cultured human corneal epithelial (HCE) cells in vitro and to the cornea of rats in vivo. The following experiments were conducted: cell counting kit 8 assay to detect cell viability; quantitative real-time PCR assay; Western blotting and immunofluorescent staining to measure gene expressions or protein levels of key reactive oxygen species (ROS)-associated factors (3-nitrotyrosine [3-NT]; nicotinamide adenine dinucleotide phosphate [NADPH]-oxidase 4 [NOX4]; superoxide dismutase [SOD]); catalase and nuclear factor [erythroid-derived 2]-like 2 [NRF2]); as well as main factors of the Wnt/β-catenin signaling pathway (p-LRP6, β-catenin and transcription factor 4 [TCF4]); histologic staining; and TUNEL staining to examine sections of rat corneas. Results:We found that SERPINA3K concentration dependently protected cell viability, decreased levels of ROS marker 3-NT, suppressed NOX4, and upregulated SOD and catalase. Furthermore, SERPINA3K inhibited the activation of the ROS pathway NRF2 and its downstream factors, NAD(P)H dehydrogenase (quinone) 1 (NQO1) and heme oxygenase 1 (HO1), and also suppressed the activation of the Wnt signaling pathway p-LRP6, β-catenin, and TCF4 in HCE cells treated with 4-HNE. Meanwhile, SERPINA3K ameliorated the oxidant injury of rat corneas induced by 4-HNE and downregulated ROS systems and the Wnt/β-catenin pathway. Conclusions:Our findings show that SERPINA3K protected the oxidant damage induced by 4-HNE in the cornea and its underlying mechanism was through suppression of the ROS system and inhibition of the activated Wnt/β-catenin signaling pathway. |
| 巻・号 | 58(7) |
| ページ | 2874-2883 |
| 公開日 | 2017-6-1 |
| DOI | 10.1167/iovs.17-21544 |
| PII | 2630894 |
| PMID | 28586911 |
| MeSH | Aldehydes / toxicity Animals Blotting, Western Cell Survival Cells, Cultured Cornea / drug effects Cornea / metabolism Cornea / pathology Corneal Diseases / chemically induced Corneal Diseases / drug therapy* Corneal Diseases / genetics Disease Models, Animal Eye Proteins / biosynthesis Eye Proteins / genetics Gene Expression Regulation Humans Kallikreins Male Oxidative Stress / drug effects* RNA / genetics Rats Rats, Wistar Reactive Oxygen Species / metabolism Real-Time Polymerase Chain Reaction Serpins / pharmacology* |
| IF | 3.47 |
| リソース情報 | |
| ヒト・動物細胞 | HCE-T(RCB2280) |