PUBLICATION

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

Authors
Cheng, K., Huang, Y., Wang, C.
ID
ZDB-PUB-211116-8
Date
2021
Source
International Journal of Molecular Sciences   22(21): (Journal)
Registered Authors
Keywords
1,25(OH)2D3, Keap1?Nrf2?GPx4, NF-?B?hepcidin, ferroptosis, zebrafish liver cells
MeSH Terms
  • NF-E2-Related Factor 2/metabolism*
  • Animals
  • Zebrafish Proteins/metabolism*
  • Mitochondria/ultrastructure
  • Lipid Peroxidation/drug effects
  • Malondialdehyde/metabolism
  • Signal Transduction/drug effects
  • Cell Line
  • Carrier Proteins/metabolism*
  • Zebrafish
  • Cell Survival/drug effects
  • Iron/metabolism
  • Cholecalciferol/pharmacology*
  • Cholecalciferol/therapeutic use
  • Ferroptosis/drug effects*
  • Reactive Oxygen Species/metabolism
  • Liver/cytology
  • Liver/drug effects
  • Liver/metabolism
  • NF-kappa B/metabolism*
  • Phospholipid Hydroperoxide Glutathione Peroxidase/antagonists & inhibitors
  • Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism*
  • Gene Expression Regulation/drug effects
  • Hepcidins/metabolism*
(all 24)
PubMed
34768761 Full text @ Int. J. Mol. Sci.
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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Citation
Cheng, K., Huang, Y., Wang, C. (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):.