Characterization of EPO H131S as a key mutation site in the hypoxia-adaptive evolution of Gymnocypris dobula

Fish Physiol Biochem. 2022 Jun;48(3):723-733. doi: 10.1007/s10695-022-01080-6. Epub 2022 May 13.

Abstract

Erythropoietin (EPO) is a glycoprotein hormone involved in proerythropoiesis, antioxidation, and antiapoptosis. It also contributes to cellular immune function in high-altitude species, such as the schizothoracine fish Gymnocypris dobula. Six mutation sites previously identified in EPO from G. dobula (GD-EPO) were injected into zebrafish embryos, and their effects were compared with EPO from the low-altitude schizothoracine Schizothorax prenanti. The key mutation site in GD-EPO was identified as H131S. Under hypoxic conditions, the levels of superoxide dismutase and malondialdehyde were decreased, whereas that of nitric oxide was increased in zebrafish injected with GD-EPO compared with those injected with S. prenanti-EPO (SP-EPO). The results suggest that EPO in high-altitude schizothoracine species is both antioxidative and antiapoptotic, driven by the H131S mutation site. Thus, this enhanced the ability of this species to adapt to the high-altitude hypoxic environment. These results provide a basis for investigating further the hypoxia adaptation mechanisms of teleosts.

Keywords: Antiapoptosis; Antioxidation; EPO; Gymnocypris dobula; H131S.

MeSH terms

  • Animals
  • Cyprinidae* / genetics
  • Erythropoietin* / genetics
  • Hypoxia / genetics
  • Mutation
  • Zebrafish

Substances

  • Erythropoietin