1,25(OH)2D3 Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis

Ke Cheng; Yanqing Huang; Chunfang Wang

doi:10.3390/ijms222111334

journal article Open Access Oct 20, 2021

1,25(OH)2D3 Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis

Ke Cheng

Yanqing Huang Chunfang Wang

International Journal of Molecular Sciences Vol. 22 No. 21 pp. 11334 · MDPI AG

View at Publisher Save 10.3390/ijms222111334

Abstract

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)2D3 on cell ferroptosis and its mechanism of action. The results showed that different incubation patterns of 1,25(OH)2D3 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)2D3 preincubation for 72 h. Preincubation of ZFL at 200 pM 1,25(OH)2D3 for 72 h downgraded keap1 and ptgs2 gene expression, increased nrf2, ho-1, fth1, gpx4a,b expression, and lowered the expression of the nf-κb p65,il-6,il-1β gene, thus reducing the expression of hamp1. The above results indicate that different incubation patterns of 1,25(OH)2D3 have protective effects on ferroptosis of ZFL induced by ferroptosis activator RSL3 and 1,25(OH)2D3 can inhibit ferroptosis of ZFL by regulating Keap1–Nrf2–GPx4 and NF-κB–hepcidin axis.

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Details

Published: Oct 20, 2021
Vol/Issue: 22(21)
Pages: 11334
License: View

Authors

K

Ke Cheng

Hubei Provincial Engineering Laboratory for Pond Aquaculture, The College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China; Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Wuhan 430070, China

Y

Yanqing Huang

East China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Shanghai 200090, China

C

Chunfang Wang

Hubei Provincial Engineering Laboratory for Pond Aquaculture, The College of Fisheries, Huazhong Agricultural University, Wuhan 430070, China; Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Wuhan 430070, China

Funding

National Natural Science Foundation of China Award: 31672667

Cite This Article

Ke Cheng, Yanqing Huang, Chunfang Wang (2021). 1,25(OH)2D3 Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis. International Journal of Molecular Sciences, 22(21), 11334. https://doi.org/10.3390/ijms222111334

1,25(OH)2D3 Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis

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