2. Academic Validation
  3. Deletion of prolyl hydroxylase domain-containing enzyme 3 (phd3) in zebrafish facilitates hypoxia tolerance

Deletion of prolyl hydroxylase domain-containing enzyme 3 (phd3) in zebrafish facilitates hypoxia tolerance

  • J Biol Chem. 2023 Nov 1:105420. doi: 10.1016/j.jbc.2023.105420.
Qian Liao 1,  Hongyan Deng 2,  Zixuan Wang 1,  Guangqing Yu 3,  Chunchun Zhu 4,  Shuke Jia 1,  Wen Liu 1,  Yao Bai 1,  Xueyi Sun 1,  Xiaoyun Chen 1,  Wuhan Xiao 5,  Xing Liu 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China; Hubei Hongshan Laboratory, Wuhan, 430070, P. R. China; University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
  • 2 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China; College of Life Science, Wuhan University, Wuhan, 430072, PR China.
  • 3 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China.
  • 4 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China; Hubei Hongshan Laboratory, Wuhan, 430070, P. R. China.
  • 5 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China; Hubei Hongshan Laboratory, Wuhan, 430070, P. R. China; University of Chinese Academy of Sciences, Beijing, 100049, P. R. China; The Innovation of Seed Design, Chinese Academy of Sciences, Wuhan, 430072, P. R. China. Electronic address: w-xiao@ihb.ac.cn.
  • 6 State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, P. R. China; University of Chinese Academy of Sciences, Beijing, 100049, P. R. China; The Innovation of Seed Design, Chinese Academy of Sciences, Wuhan, 430072, P. R. China. Electronic address: liuxing@ihb.ac.cn.
PMID: 37923141 DOI: 10.1016/j.jbc.2023.105420
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.

Keywords

hif-1α; hif-2α; hypoxia; phd3; zebrafish.

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