Maresin-1 inhibits high glucose induced ferroptosis in ARPE-19 cells by activating the Nrf2/HO-1/GPX4 pathway
Abstract Background Maresin-1 plays an important role in diabetic illnesses and ferroptosis is associated with pathogenic processes of diabetic retinopathy (DR). The goal of this study is to explore the influence of maresin-1 on ferroptosis and its molecular mechanism in DR. Methods ARPE-19 cells we...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | BMC Ophthalmology |
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| Online Access: | https://doi.org/10.1186/s12886-023-03115-9 |
| _version_ | 1827723920102391808 |
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| author | Yufei Li Jieyu Liu Xibo Ma Xue Bai |
| author_facet | Yufei Li Jieyu Liu Xibo Ma Xue Bai |
| author_sort | Yufei Li |
| collection | DOAJ |
| description | Abstract Background Maresin-1 plays an important role in diabetic illnesses and ferroptosis is associated with pathogenic processes of diabetic retinopathy (DR). The goal of this study is to explore the influence of maresin-1 on ferroptosis and its molecular mechanism in DR. Methods ARPE-19 cells were exposed to high glucose (HG) condition for developing a cellular model of DR. The CCK-8 assay and flow cytometry were used to assess ARPE-19 cell proliferation and apoptosis, respectively. Furthermore, the GSH content, MDA content, ROS level, and Fe2+ level were measured by using a colorimetric GSH test kit, a Lipid Peroxidation MDA Assay Kit, a DCFH-DA assay and the phirozine technique, respectively. Immunofluorescence labelling was used to detect protein levels of ACSL4 and PTGS2. Messenger RNA and protein expression of HO-1, GPX4 and Nrf2 was evaluated through western blotting and quantitative real time-polymerase chain reaction (qRT-PCR). To establish a diabetic mouse model, mice were intraperitoneally injected 150 mg/kg streptozotocin. The MDA content, ROS level and the iron level were detected by using corresponding commercial kits. Results Maresin-1 promoted cell proliferation while reducing the apoptotic process in HG-induced ARPE-19 cells. Maresin-1 significantly reduced ferroptosis induced by HG in ARPE-19 cells, as demonstrated as a result of decreased MDA content, ROS level, Fe2+ level, PTGS2 expression, ACSL4 expression and increased GSH content. With respect to mechanisms, maresin-1 treatment up-regulated the mRNA expression and protein expression of HO-1, GPX4 and Nrf2 in HG-induced ARPE-19 cells. Nrf2 inhibitor reversed the inhibitory effects of maresin-1 on ferroptosis in HG-induced ARPE-19 cells. In vivo experiments, we found that Maresin-1 evidently repressed ferroptosis a mouse model of DR, as evidenced by the decreased MDA content, ROS level and iron level in retinal tissues of mice. Conclusion Maresin-1 protects ARPE cells from HG-induced ferroptosis via activating the Nrf2/HO-1/GPX4 pathway, suggesting that maresin-1 prevents DR development. |
| first_indexed | 2024-03-10T22:07:34Z |
| format | Article |
| id | doaj.art-a0d4df0109f44ce38754bad52a4806fb |
| institution | Directory Open Access Journal |
| issn | 1471-2415 |
| language | English |
| last_indexed | 2024-03-10T22:07:34Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
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| spelling | doaj.art-a0d4df0109f44ce38754bad52a4806fb2023-11-19T12:45:15ZengBMCBMC Ophthalmology1471-24152023-09-0123111010.1186/s12886-023-03115-9Maresin-1 inhibits high glucose induced ferroptosis in ARPE-19 cells by activating the Nrf2/HO-1/GPX4 pathwayYufei Li0Jieyu Liu1Xibo Ma2Xue Bai3Ophthalmology Department, Zhongshan Hospital Affiliated to Xiamen UniversityEndocrinology Department, Beijing Electric Power HospitalOtorhinolaryngology Department, Jilin Province People’s HospitalOphthalmology Department, Zhongshan Hospital Affiliated to Xiamen UniversityAbstract Background Maresin-1 plays an important role in diabetic illnesses and ferroptosis is associated with pathogenic processes of diabetic retinopathy (DR). The goal of this study is to explore the influence of maresin-1 on ferroptosis and its molecular mechanism in DR. Methods ARPE-19 cells were exposed to high glucose (HG) condition for developing a cellular model of DR. The CCK-8 assay and flow cytometry were used to assess ARPE-19 cell proliferation and apoptosis, respectively. Furthermore, the GSH content, MDA content, ROS level, and Fe2+ level were measured by using a colorimetric GSH test kit, a Lipid Peroxidation MDA Assay Kit, a DCFH-DA assay and the phirozine technique, respectively. Immunofluorescence labelling was used to detect protein levels of ACSL4 and PTGS2. Messenger RNA and protein expression of HO-1, GPX4 and Nrf2 was evaluated through western blotting and quantitative real time-polymerase chain reaction (qRT-PCR). To establish a diabetic mouse model, mice were intraperitoneally injected 150 mg/kg streptozotocin. The MDA content, ROS level and the iron level were detected by using corresponding commercial kits. Results Maresin-1 promoted cell proliferation while reducing the apoptotic process in HG-induced ARPE-19 cells. Maresin-1 significantly reduced ferroptosis induced by HG in ARPE-19 cells, as demonstrated as a result of decreased MDA content, ROS level, Fe2+ level, PTGS2 expression, ACSL4 expression and increased GSH content. With respect to mechanisms, maresin-1 treatment up-regulated the mRNA expression and protein expression of HO-1, GPX4 and Nrf2 in HG-induced ARPE-19 cells. Nrf2 inhibitor reversed the inhibitory effects of maresin-1 on ferroptosis in HG-induced ARPE-19 cells. In vivo experiments, we found that Maresin-1 evidently repressed ferroptosis a mouse model of DR, as evidenced by the decreased MDA content, ROS level and iron level in retinal tissues of mice. Conclusion Maresin-1 protects ARPE cells from HG-induced ferroptosis via activating the Nrf2/HO-1/GPX4 pathway, suggesting that maresin-1 prevents DR development.https://doi.org/10.1186/s12886-023-03115-9Maresin-1Diabetic retinopathyFerroptosisNuclear factor erythroid 2-related factor 2 |
| spellingShingle | Yufei Li Jieyu Liu Xibo Ma Xue Bai Maresin-1 inhibits high glucose induced ferroptosis in ARPE-19 cells by activating the Nrf2/HO-1/GPX4 pathway BMC Ophthalmology Maresin-1 Diabetic retinopathy Ferroptosis Nuclear factor erythroid 2-related factor 2 |
| title | Maresin-1 inhibits high glucose induced ferroptosis in ARPE-19 cells by activating the Nrf2/HO-1/GPX4 pathway |
| title_full | Maresin-1 inhibits high glucose induced ferroptosis in ARPE-19 cells by activating the Nrf2/HO-1/GPX4 pathway |
| title_fullStr | Maresin-1 inhibits high glucose induced ferroptosis in ARPE-19 cells by activating the Nrf2/HO-1/GPX4 pathway |
| title_full_unstemmed | Maresin-1 inhibits high glucose induced ferroptosis in ARPE-19 cells by activating the Nrf2/HO-1/GPX4 pathway |
| title_short | Maresin-1 inhibits high glucose induced ferroptosis in ARPE-19 cells by activating the Nrf2/HO-1/GPX4 pathway |
| title_sort | maresin 1 inhibits high glucose induced ferroptosis in arpe 19 cells by activating the nrf2 ho 1 gpx4 pathway |
| topic | Maresin-1 Diabetic retinopathy Ferroptosis Nuclear factor erythroid 2-related factor 2 |
| url | https://doi.org/10.1186/s12886-023-03115-9 |
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