Hu Ruiqin, Li Genfang, Xu Qianghua, Chen Liangbiao
International Joint Research Centre for Marine Biosciences (Ministry of Science and Technology), College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources (Ministry of Education) and International Research Centre for Marine Biosciences, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
Front Physiol. 2022 Aug 26;13:925752. doi: 10.3389/fphys.2022.925752. eCollection 2022.
Acute hypoxia in water has always been a thorny problem in aquaculture. Oxygen and iron play important roles and are interdependent in fish. Iron is essential for oxygen transport and its concentration tightly controlled to maintain the cellular redox homeostasis. However, it is still unclear the role and mechanism of iron in hypoxic stress of fish. In this study, we investigated the role of iron in hypoxic responses of two zebrafish-derived cell lines. We found hypoxia exposed zebrafish liver cells (ZFL) demonstrated reduced expression of Ferritin and the gene for mitochondrial iron storage, corresponding to reduction of both intracellular and mitochondrial free iron and significant decrease of ROS levels in multiple cellular components, including mitochondrial ROS and lipid peroxidation level. In parallel, the mitochondrial integrity was severely damaged. Addition of exogenous iron restored the iron and ROS levels in cellular and mitochondria, reduced mitochondrial damage through enhancing mitophagy leading to higher cell viability, while treated the cells with iron chelator (DFO) or ferroptosis inhibitor (Fer-1) showed no improvements of the cellular conditions. In contrast, in hypoxia insensitive zebrafish embryonic fibroblasts cells (ZF4), the expression of genes related to iron metabolism showed opposite trends of change and higher mitochondrial ROS level compared with the ZFL cells. These results suggest that iron homeostasis is important for zebrafish cells to maintain mitochondrial integrity in hypoxic stress, which is cell type dependent. Our study enriched the hypoxia regulation mechanism of fish, which helped to reduce the hypoxia loss in fish farming.
水中急性缺氧一直是水产养殖中的棘手问题。氧气和铁在鱼类中发挥着重要作用且相互依存。铁对于氧气运输至关重要，其浓度受到严格控制以维持细胞氧化还原稳态。然而，铁在鱼类低氧应激中的作用和机制仍不清楚。在本研究中，我们调查了铁在两种斑马鱼来源细胞系低氧反应中的作用。我们发现缺氧暴露的斑马鱼肝细胞（ZFL）显示铁蛋白和线粒体铁储存基因的表达降低，这与细胞内和线粒体内游离铁的减少以及多个细胞成分中活性氧水平的显著降低相对应，包括线粒体活性氧和脂质过氧化水平。同时，线粒体完整性受到严重破坏。添加外源铁可恢复细胞和线粒体中的铁和活性氧水平，通过增强线粒体自噬减少线粒体损伤，从而提高细胞活力，而用铁螯合剂（DFO）或铁死亡抑制剂（Fer-1）处理细胞则未改善细胞状况。相反，在对低氧不敏感的斑马鱼胚胎成纤维细胞（ZF4）中，与铁代谢相关的基因表达呈现相反的变化趋势，且线粒体活性氧水平高于ZFL细胞。这些结果表明，铁稳态对于斑马鱼细胞在低氧应激下维持线粒体完整性很重要，这是细胞类型依赖性的。我们的研究丰富了鱼类的低氧调节机制，有助于减少养鱼业中的低氧损失。
