Physiological and transcriptomic analysis revealed the alleviating effect of 1,25(OH)2D3 on environmental iron overloading induced ferroptosis in zebrafish*
文献类型： 外文期刊
作者： Cheng, Ke 1 ; Yang, Gang 1 ; Huang, Min 1 ; Wang, Yijia 1 ; Huang, Yanqing 4 ; Wang, Chunfang 1 ;
作者机构： 1.Huazhong Agr Univ, Coll Fisheries, Wuhan 430070, Peoples R China
2.Minist Educ, Engn Res Ctr Green Dev Convent Aquat Biol Ind Yang, Wuhan 430070, Peoples R China
3.Hubei Prov Engn Lab Pond Aquaculture, Wuhan 430070, Peoples R China
4.Chinese Acad Fishery Sci, East China Sea Fisheries Res Inst, Shanghai 200090, Peoples R China
5.Huazhong Agr Univ, Coll Fisheries, Shizishan Rd, Wuhan 430070, Hubei, Peoples R China
关键词： 25(OH) 2 D 3; Iron overload; Ferroptosis; Metabolic disorders; Antioxidant
期刊名称：ENVIRONMENTAL POLLUTION （ 影响因子：8.9； 五年影响因子：9.5 ）
ISSN： 0269-7491
年卷期： 2024 年 346 卷
页码：
收录情况： SCI
摘要： Iron overload in the aquatic environment can cause damage in fish bodies. Vitamin D3 (VD3) has been proven to have antioxidant and regulatory effects on iron transport. The current research investigated the effects of environmental iron overload on larval zebrafish and explored the effects of 1,25(OH)2D3 on ferroptosis in zebrafish larvae and zebrafish liver cells (ZFL) caused by iron overload in the environment and its possible regulatory mechanisms. The results showed that 1,25(OH)2D3 alleviated liver damage in zebrafish larvae and mitochondrial damage in ZFL after excessive ammonium ferric citrate (FAC) treatment, and improved the survival rate of ZFL. 1,25(OH)2D3 cleared and inhibited excessive FAC induced abnormal accumulation of ROS, lipid ROS, MDA, and Fe2+ in zebrafish larvae and ZFL, as well as enhanced the activity of antioxidant enzyme GPx4. Transcriptomic analysis showed that 1,25(OH)2D3 can regulate ferroptosis in ZFL by regulating signaling pathways related to oxidative stress, iron homeostasis, mitochondrial function, and ERS, mainly including ferroptosis, neoptosis, p53 signaling pathway, apoptosis, FoxO signaling pathway. Validation of transcriptome data showed that 1,25(OH)2D3 inhibits ferroptosis in zebrafish larvae and ZFL caused by excessive FAC via promoting the expression of slc40a1 and hmox1a genes and increasing SLC40A1 protein levels. In summary, 1,25(OH)2D3 can resist ferroptosis in zebrafish caused by iron overload in the environment mainly via regulating antioxidant capacity and iron ion transport.
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