1,25(OH)<sub>2</sub>D<sub>3</sub> Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis

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 mod...

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Autores principales:	Ke Cheng, Yanqing Huang, Chunfang Wang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	ferroptosis 1,25(OH)<sub>2</sub>D<sub>3</sub> zebrafish liver cells Keap1–Nrf2–GPx4 NF-κB–hepcidin Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/6e448005ed844931ac5bfe5a3bd6541d
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spelling	oai:doaj.org-article:6e448005ed844931ac5bfe5a3bd6541d2021-11-11T16:48:50Z1,25(OH)<sub>2</sub>D<sub>3</sub> Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis10.3390/ijms2221113341422-00671661-6596https://doaj.org/article/6e448005ed844931ac5bfe5a3bd6541d2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11334https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Ferroptosis 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)<sub>2</sub>D<sub>3</sub> on cell ferroptosis and its mechanism of action. The results showed that different incubation patterns of 1,25(OH)<sub>2</sub>D<sub>3</sub> 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)<sub>2</sub>D<sub>3</sub> preincubation for 72 h. Preincubation of ZFL at 200 pM 1,25(OH)<sub>2</sub>D<sub>3</sub> for 72 h downgraded <i>keap1</i> and <i>ptgs2</i> gene expression, increased <i>nrf2, ho-1, fth1, gpx4a,b</i> expression, and lowered the expression of the <i>nf-κb p65,il-6,il-1β</i> gene, thus reducing the expression of <i>hamp1.</i> The above results indicate that different incubation patterns of 1,25(OH)<sub>2</sub>D<sub>3</sub> have protective effects on ferroptosis of ZFL induced by ferroptosis activator RSL3 and 1,25(OH)<sub>2</sub>D<sub>3</sub> can inhibit ferroptosis of ZFL by regulating Keap1–Nrf2–GPx4 and NF-κB–hepcidin axis.Ke ChengYanqing HuangChunfang WangMDPI AGarticleferroptosis1,25(OH)<sub>2</sub>D<sub>3</sub>zebrafish liver cellsKeap1–Nrf2–GPx4NF-κB–hepcidinBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11334, p 11334 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ferroptosis 1,25(OH)<sub>2</sub>D<sub>3</sub> zebrafish liver cells Keap1–Nrf2–GPx4 NF-κB–hepcidin Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	ferroptosis 1,25(OH)<sub>2</sub>D<sub>3</sub> zebrafish liver cells Keap1–Nrf2–GPx4 NF-κB–hepcidin Biology (General) QH301-705.5 Chemistry QD1-999 Ke Cheng Yanqing Huang Chunfang Wang 1,25(OH)<sub>2</sub>D<sub>3</sub> Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis
description	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)<sub>2</sub>D<sub>3</sub> on cell ferroptosis and its mechanism of action. The results showed that different incubation patterns of 1,25(OH)<sub>2</sub>D<sub>3</sub> 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)<sub>2</sub>D<sub>3</sub> preincubation for 72 h. Preincubation of ZFL at 200 pM 1,25(OH)<sub>2</sub>D<sub>3</sub> for 72 h downgraded <i>keap1</i> and <i>ptgs2</i> gene expression, increased <i>nrf2, ho-1, fth1, gpx4a,b</i> expression, and lowered the expression of the <i>nf-κb p65,il-6,il-1β</i> gene, thus reducing the expression of <i>hamp1.</i> The above results indicate that different incubation patterns of 1,25(OH)<sub>2</sub>D<sub>3</sub> have protective effects on ferroptosis of ZFL induced by ferroptosis activator RSL3 and 1,25(OH)<sub>2</sub>D<sub>3</sub> can inhibit ferroptosis of ZFL by regulating Keap1–Nrf2–GPx4 and NF-κB–hepcidin axis.
format	article
author	Ke Cheng Yanqing Huang Chunfang Wang
author_facet	Ke Cheng Yanqing Huang Chunfang Wang
author_sort	Ke Cheng
title	1,25(OH)<sub>2</sub>D<sub>3</sub> Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis
title_short	1,25(OH)<sub>2</sub>D<sub>3</sub> Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis
title_full	1,25(OH)<sub>2</sub>D<sub>3</sub> Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis
title_fullStr	1,25(OH)<sub>2</sub>D<sub>3</sub> Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis
title_full_unstemmed	1,25(OH)<sub>2</sub>D<sub>3</sub> Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis
title_sort	1,25(oh)<sub>2</sub>d<sub>3</sub> inhibited ferroptosis in zebrafish liver cells (zfl) by regulating keap1-nrf2-gpx4 and nf-κb-hepcidin axis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6e448005ed844931ac5bfe5a3bd6541d
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1,25(OH)<sub>2</sub>D<sub>3</sub> Inhibited Ferroptosis in Zebrafish Liver Cells (ZFL) by Regulating Keap1-Nrf2-GPx4 and NF-κB-hepcidin Axis

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