Deletion of the <i>foxO4</i> Gene Increases Hypoxia Tolerance in Zebrafish
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 invol...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/10/8942 |
| Summary: | 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 <i>foxO4</i> in the hypoxia response, we detected the expression of <i>foxO4</i> and the regulatory relationship between Hif1α and <i>foxO4</i> under hypoxic conditions. It was found that the expression of <i>foxO4</i> was up-regulated in ZF4 cells and zebrafish tissues after hypoxia treatment, and Hif1α could directly target the HRE of the <i>foxO4</i> promoter to regulate <i>foxO4</i> transcription, indicating that <i>foxO4</i> was involved in the hypoxia response by the Hif1α-mediated pathway. Furthermore, we obtained <i>foxO4</i> knockout zebrafish and found that the disruption of <i>foxO4</i> increased the tolerance to hypoxia. Further research found that the oxygen consumption and locomotor activity of <i>foxO4</i><sup>−/−</sup> zebrafish were lower than those of WT zebrafish, as was true for NADH content, NADH/NAD<sup>+</sup> rate, and expression of mitochondrial respiratory chain complex-related genes. This suggests that disruption of <i>foxO4</i> reduced the oxygen demand threshold of the organism, which explained why the <i>foxO4<sup>−/−</sup></i> zebrafish were more tolerant to hypoxia than WT zebrafish. These results will provide a theoretical basis for further study of the role of <i>foxO4</i> in the hypoxia response. |
|---|---|
| ISSN: | 1661-6596 1422-0067 |