Key Lab of Freshwater Animal Breeding/Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Fishery, Huazhong Agricultural University, Wuhan 430070, China.
Engineering Research Center of Green Development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education, Wuhan 430070, China.
Int J Mol Sci. 2023 May 18;24(10):8942. doi: 10.3390/ijms24108942.
Oxygen homeostasis is an important organizing principle for understanding development, physiology, disease, and evolution. Under various physiological and pathological states, organisms experience oxygen deficiency or hypoxia. FoxO4 has been recognized as an important transcriptional regulator involved in a variety of cellular functions, including proliferation, apoptosis, differentiation, and stress resistance, but its role in hypoxia adaptation mechanisms in animals is not so clear. To explore the role of in the hypoxia response, we detected the expression of and the regulatory relationship between Hif1α and under hypoxic conditions. It was found that the expression of was up-regulated in ZF4 cells and zebrafish tissues after hypoxia treatment, and Hif1α could directly target the HRE of the promoter to regulate transcription, indicating that was involved in the hypoxia response by the Hif1α-mediated pathway. Furthermore, we obtained knockout zebrafish and found that the disruption of increased the tolerance to hypoxia. Further research found that the oxygen consumption and locomotor activity of zebrafish were lower than those of WT zebrafish, as was true for NADH content, NADH/NAD rate, and expression of mitochondrial respiratory chain complex-related genes. This suggests that disruption of reduced the oxygen demand threshold of the organism, which explained why the zebrafish were more tolerant to hypoxia than WT zebrafish. These results will provide a theoretical basis for further study of the role of in the hypoxia response.
氧平衡是理解发育、生理、疾病和进化的重要原则。在各种生理和病理状态下，生物体都会经历缺氧或低氧。FoxO4 已被认为是一种重要的转录调节因子，参与多种细胞功能，包括增殖、凋亡、分化和应激抵抗，但它在动物低氧适应机制中的作用尚不清楚。为了探讨在低氧反应中的作用，我们检测了在低氧条件下的表达以及 Hif1α 和之间的调控关系。结果发现，在 ZF4 细胞和斑马鱼组织中，缺氧处理后表达上调，并且 Hif1α 可以直接靶向的 HRE 来调节转录，这表明通过 Hif1α 介导的途径参与了低氧反应。此外，我们获得了缺失的斑马鱼，并发现的破坏增加了对低氧的耐受性。进一步的研究发现，缺失的斑马鱼的耗氧量和运动活性低于 WT 斑马鱼，NADH 含量、NADH/NAD 比率和线粒体呼吸链复合物相关基因的表达也是如此。这表明破坏降低了机体的氧需求阈值，这解释了为什么缺失的斑马鱼比 WT 斑马鱼更能耐受低氧。这些结果将为进一步研究在低氧反应中的作用提供理论基础。
