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Hypoxia-inducible factor 1α from a high-altitude fish enhances cytoprotection and elevates nitric oxide production in hypoxic environment

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Abstract

Hypoxia-inducible factors (HIFs) are master transcription factor regulating hypoxic responses in vertebrates. Species of Schizothoracine, a sub-family of cyprinidae, are highly endemic to the hypoxic Qinghai-Tibetan Plateau (QTP). What roles the HIFs play in hypoxic adaptation in the Schizothoracine fish is little known. In this study, the HIF-1α/B gene from Gymnocypris dobula (Gd) was characterized. The predicted protein for Gd-HIF-1α/B contains the main domains (bHLH, PAS, PAC, ODD, N-TAD, and C-TAD). Moreover, a specific mutation that the proline hydroxylation motif (LXXLAP) mutated into PxxLAP was observed in Gd-HIF-1α/B CODD domain, which may lead to changes in the function. To clarify whether HIF-1α/B of G. dobula possesses hypoxic adaptive features, Gd-HIF1α/B and Schizothorax prenanti-HIF1α/B (Sp-HIF1α/B) were cloned into an expression vector and transfected into 293T cells. Cell viability was found to be significantly higher in cells transfected with Gd-HIF-1α/B than those transfected with Sp-HIF-1α/B under hypoxic conditions. In addition, G. dobula HIF-1α/B showed stronger activity in transactivating the expression of nitric oxide (NO)–synthesizing enzyme, NOS2B under hypoxia stresses than the orthologous gene from S. prenanti, which were accompanied with upregulated expressions of NOS2B in heart of G. dobula, which may attribute to elevated NO levels detected in G. dobula than the lower land species. These results indicated that the HIF-1α plays an important role in mediating the iNOS signaling system in the process of evolutionary adaptation of the Schizothoracine to the highland environment.

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Acknowledgments

We would like to thank all of the people in the Yadong Forestry Bureau, Tibet, for the sample collection.

Funding

This work was supported in part by the Research Project of the Chinese Ministry of Education (no. 213013A), the National Natural Science Foundation of China (grant no. 31772826), the National Natural Science Foundation of China (grant no. 31572598), the National Natural Science Foundation of China (grant no. 31572611), and the National Natural Science Foundation of China (grant no. 31702312).

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Authors and Affiliations

  1. Key Laboratory of Sustainable Exploitation of Oceanic Fisheries Resources, Ministry of Education, College of Marine Sciences, Shanghai Ocean University, 999 Huchenghuan Road, Lingang New City, Shanghai, 201306, People’s Republic of China

    Congcong Wang, Xiaohui Wu, Xingxing Hu, Huapeng Jiang & Qianghua Xu

  2. Key Laboratory of Aquaculture Resources and Utilization, Ministry of Education, College of Fisheries and Life Sciences, Shanghai Ocean University, 999 Huchenghuan Road, Lingang New City, Shanghai, 201306, People’s Republic of China

    Congcong Wang & Liangbiao Chen

  3. National Distant-water Fisheries Engineering Research Center, Shanghai Ocean University, Shanghai, 201306, People’s Republic of China

    Qianghua Xu

  4. Collaborative Innovation Center for Distant-water Fisheries, Shanghai, 201306, China

    Qianghua Xu

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  1. Congcong Wang
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  2. Xiaohui Wu
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  3. Xingxing Hu
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  4. Huapeng Jiang
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Correspondence to Liangbiao Chen or Qianghua Xu.

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Experimental protocols involving live animals were approved by the Ethics Committee for the Use of Animal Subjects of Shanghai Ocean University.

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Congcong Wang and Xiaohu Wu are co-first authors.

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Wang, C., Wu, X., Hu, X. et al. Hypoxia-inducible factor 1α from a high-altitude fish enhances cytoprotection and elevates nitric oxide production in hypoxic environment. Fish Physiol Biochem 46, 39–49 (2020). https://doi.org/10.1007/s10695-019-00694-7

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