2. Academic Validation
  3. Maresin-1 inhibits high glucose induced ferroptosis in ARPE-19 cells by activating the Nrf2/HO-1/GPX4 pathway

Maresin-1 inhibits high glucose induced ferroptosis in ARPE-19 cells by activating the Nrf2/HO-1/GPX4 pathway

  • BMC Ophthalmol. 2023 Sep 6;23(1):368. doi: 10.1186/s12886-023-03115-9.
Yufei Li 1,  Jieyu Liu 2,  Xibo Ma 3,  Xue Bai 4
Affiliations

Affiliations

  • 1 Ophthalmology Department, Zhongshan Hospital Affiliated to Xiamen University, No.201-209 Hubinnan Road, Siming District, 361004, Xiamen, China.
  • 2 Endocrinology Department, Beijing Electric Power Hospital, 100073, Beijing, China.
  • 3 Otorhinolaryngology Department, Jilin Province People's Hospital, 130000, Changchun, China.
  • 4 Ophthalmology Department, Zhongshan Hospital Affiliated to Xiamen University, No.201-209 Hubinnan Road, Siming District, 361004, Xiamen, China. baixue_zhxu@163.com.
PMID: 37674121 DOI: 10.1186/s12886-023-03115-9
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.

Keywords

Diabetic retinopathy; Ferroptosis; Maresin-1; Nuclear factor erythroid 2-related factor 2.

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