Abstract：
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.
摘要：
水生环境中的铁过载会对鱼体造成损害。维生素D3（VD3）已被证明对铁运输具有抗氧化和调节作用。本研究考察了环境铁过载对斑马鱼幼体的影响,探讨了1,25(OH)2D3对环境中铁过载引起的斑马鱼幼体和斑马鱼肝细胞(ZFL)铁凋亡的影响及其可能的调控机制。结果表明，1,25(OH)2D3减轻了过量柠檬酸铁铵(FAC)处理后斑马鱼幼虫的肝损伤和ZFL的线粒体损伤，提高了ZFL的存活率。1,25(OH)2D3清除并抑制过量FAC诱导的ROS异常积累,脂质ROS，MDA,斑马鱼幼虫和ZFL中的Fe2+，以及增强抗氧化酶GPx4的活性。转录组学分析表明,1,25(OH)2D3可通过调节氧化应激相关信号通路来调节ZFL中的铁细胞凋亡,铁稳态，线粒体功能，和ERS,主要包括铁性凋亡，新生，p53信号通路,凋亡，FoxO信号通路。转录组数据的验证表明，1,25（OH）2D3通过促进slc40a1和hmox1a基因的表达和增加SLC40A1蛋白水平来抑制由过度FAC引起的斑马鱼幼虫和ZFL的铁凋亡。总之,1,25(OH)2D3主要通过调节抗氧化能力和铁离子的转运来抵抗环境中铁过载引起的斑马鱼铁凋亡。
