Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China; National Aquatic Animal Diseases Para-reference Laboratory (HZAU), Wuhan, 430070, China.
Department of Aquatic Animal Medicine, College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China.
Fish Shellfish Immunol. 2024 Nov;154:109927. doi: 10.1016/j.fsi.2024.109927. Epub 2024 Sep 28.
Aeromonas hydrophila infection is a severe, acute, and life-threatening disease affecting grass carp (Ctenopharyngodon idella) in aquaculture. Ferroptosis is a novel form of cell death characterized by the accumulation of free iron and harmful lipid peroxides within cells. While selenomethionine (Se-Met) is known to effectively inhibit ferroptosis and alleviate cell damage, its ability to counteract oxidative stress and ferroptosis induced by A. hydrophila remains unclear. The objective of this study is to reveal the possible mechanism behind the ferroptosis phenomenon during A. hydrophila infection. We established a macrophage model of A. hydrophila invasion to monitor the dynamic changes in iron metabolism markers to evaluate the correlation between ferroptotic stress and A. hydrophila infection. A. hydrophila infection induces cytotoxicity and mitochondrial membrane damage via ferroptosis. This damage is attributed to the accumulation of lipid peroxides due to intracellular ferrous ion overload and glutathione depletion. Supplementation of Se-Met reduced mitochondrial damage, enhanced antioxidant enzyme activity and reduced ferroptosis by activating the Nrf2/HO1/GPX4 axis. These findings provide new insights into the regulatory mechanisms of A. hydrophila-induced ferroptosis in teleosts and suggest that targeted inhibition of ferroptosis may offer a novel therapeutic strategy for managing A. hydrophila infections.
嗜水气单胞菌感染是一种严重的、急性的、危及生命的疾病，会影响水产养殖中的草鱼（Ctenopharyngodon idella）。铁死亡是一种新型的细胞死亡形式，其特征是细胞内自由铁和有害脂质过氧化物的积累。虽然硒代蛋氨酸（Se-Met）已被证实可有效抑制铁死亡并减轻细胞损伤，但它对抗由嗜水气单胞菌引起的氧化应激和铁死亡的能力尚不清楚。本研究旨在揭示嗜水气单胞菌感染期间铁死亡现象的可能机制。我们建立了嗜水气单胞菌侵袭的巨噬细胞模型，以监测铁代谢标志物的动态变化，评估铁死亡应激与嗜水气单胞菌感染之间的相关性。嗜水气单胞菌感染通过铁死亡诱导细胞毒性和线粒体膜损伤。这种损伤归因于细胞内亚铁离子过载和谷胱甘肽耗竭导致的脂质过氧化物积累。补充 Se-Met 通过激活 Nrf2/HO1/GPX4 轴减少线粒体损伤、增强抗氧化酶活性和减少铁死亡。这些发现为鱼类中嗜水气单胞菌诱导的铁死亡的调控机制提供了新的见解，并表明靶向抑制铁死亡可能为治疗嗜水气单胞菌感染提供一种新的治疗策略。
