PUBLICATION
Deletion of prolyl hydroxylase domain-containing enzyme 3 (phd3) in zebrafish facilitates hypoxia tolerance
- Authors
- Liao, Q., Deng, H., Wang, Z., Yu, G., Zhu, C., Jia, S., Liu, W., Bai, Y., Sun, X., Chen, X., Xiao, W., Liu, X.
- ID
- ZDB-PUB-231106-4
- Date
- 2023
- Source
- The Journal of biological chemistry 299(12): 105420 (Journal)
- Registered Authors
- Xiao, Wuhan, Yu, Guangqing
- Keywords
- hif-1α, hif-2α, hypoxia, phd3, zebrafish
- MeSH Terms
-
- Animals
- Hypoxia
- Hypoxia-Inducible Factor 1, alpha Subunit
- Hypoxia-Inducible Factor-Proline Dioxygenases/genetics
- Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism
- Procollagen-Proline Dioxygenase/genetics
- Procollagen-Proline Dioxygenase/metabolism
- Proline
- Prolyl Hydroxylases*
- Zebrafish*/metabolism
- PubMed
- 37923141 Full text @ J. Biol. Chem.
Citation
Liao, Q., Deng, H., Wang, Z., Yu, G., Zhu, C., Jia, S., Liu, W., Bai, Y., Sun, X., Chen, X., Xiao, W., Liu, X. (2023) Deletion of prolyl hydroxylase domain-containing enzyme 3 (phd3) in zebrafish facilitates hypoxia tolerance. The Journal of biological chemistry. 299(12):105420.
Abstract
Prolyl hydroxylase domain (PHD)-containing enzyme 3 (PHD3) belongs to the Caenorhabditis elegans gene egl-9 family of prolyl hydroxylases. PHD3 catalyzes proline hydroxylation of hypoxia-inducible factor α (HIF-α) and promotes HIF-α proteasomal degradation through coordination with the pVHL complex under normoxic conditions. However, the relationship between PHD3 and the hypoxic response is not well understood. In this study, we used quantitative real-time PCR assay and O-dianisidine staining to characterize the hypoxic response in zebrafish deficient in phd3. We found that the hypoxia-responsive genes are upregulated and the number of erythrocytes was increased in phd3-null zebrafish compared with their wildtype siblings. On the other hand, we show overexpression of phd3 suppresses HIF-transcriptional activation. In addition, we demonstrate phd3 promotes polyubiquitination of zebrafish hif-1/2α proteins, leading to their proteasomal degradation. Finally, we found that compared with wildtype zebrafish, phd3-null zebrafish are more resistant to hypoxia treatment. Therefore, we conclude phd3 has a role in hypoxia tolerance. These results highlight the importance of modulation of the hypoxia signaling pathway by phd3 in hypoxia adaptation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping