1,25(OH)(2)D-3 Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-kappa B-hepcidin Axis

文献类型： 外文期刊

第一作者： Cheng, Ke

作者： Cheng, Ke;Wang, Chunfang;Cheng, Ke;Wang, Chunfang;Huang, Yanqing

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关键词： ferroptosis; 1,25(OH)(2)D-3; zebrafish liver cells; Keap1-Nrf2-GPx4; NF-?B-hepcidin

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES （ 影响因子：5.924； 五年影响因子：6.132 ）

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年卷期： 2021 年 22 卷 21 期

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收录情况： SCI

摘要： Ferroptosis is a kind of iron-dependent programed cell death. Vitamin D has been shown to be an antioxidant and a regulator of iron metabolism, but the relationship between vitamin D and ferroptosis is poorly studied in fish. This study used zebrafish liver cells (ZFL) to establish a ferroptosis model to explore the effect of 1,25(OH)(2)D-3 on cell ferroptosis and its mechanism of action. The results showed that different incubation patterns of 1,25(OH)(2)D-3 improved the survival rate of ZFL, mitigated mitochondrial damage, enhanced total glutathione peroxidase (GPx) activity, and reduced intracellular reactive oxygen species (ROS), lipid peroxidation (LPO), and malondialdehyde (MDA), as well as iron ion levels, with the best effect at 200 pM 1,25(OH)(2)D-3 preincubation for 72 h. Preincubation of ZFL at 200 pM 1,25(OH)(2)D-3 for 72 h downgraded keap1 and ptgs2 gene expression, increased nrf2, ho-1, fth1, gpx4a,b expression, and lowered the expression of the nf-kappa b p65,il-6,il-1 beta gene, thus reducing the expression of hamp1. The above results indicate that different incubation patterns of 1,25(OH)(2)D-3 have protective effects on ferroptosis of ZFL induced by ferroptosis activator RSL3 and 1,25(OH)(2)D-3 can inhibit ferroptosis of ZFL by regulating Keap1-Nrf2-GPx4 and NF-kappa B-hepcidin axis.

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