Erythropoietin: friend and foe!

Our knowledge of the erythropoietin (Epo) molecule has come a long way since Carnot and Deflandre’s landmark observations, over a century ago, attributing the increase in red blood cells to a factor called ‘hemopoietin’. For decades, the scientific community thought that the role of Epo was limited to red blood cell production. However, since the mid 1990s, Epo has been shown to exert numerous extrahematopoietic effects (see Fig. 1 – ‘Traditional’). Just as one could have thought that we knew everything about this molecule, Bailey et al. (2014) have demonstrated that recombinant Epo (rHuEpo) can equally serve as a very potent antioxidant (see Fig. 1 – ‘Evolving’). Indeed, in the current issue of Acta Physiologica, we learn how the authors utilized in the first instance an in vitro approach to demonstrate the antioxidant characteristics of the rHuEpo molecule, which was then followed up by an in vivo experiment that involved exposing healthy volunteers to 12 h of hypoxia ( 13% oxygen) (Bailey et al. 2014). In the in vitro arm, the authors demonstrated that rHuEpo is a potent scavenger of the hydroxyl radical (HO ̇), both directly and indirectly, subsequent to catalytic iron chelation. The hydroxyl radical is able to react with any biological molecule inducing cellular damage and as such has been linked with vascular ageing (Bailey et al. 2010). For the human study, the authors decided to take advantage of inspiratory hypoxia, a model they previously used to induce both erythropoiesis and oxidative–nitrosative stress (Bailey et al. 2014). Exposure to hypoxia revealed that the increase in endogenous Epo can help maintain redox homeostasis by limiting the increase in oxidative–nitrosative stress through its antioxidant function. From a functional point of view, it therefore appears that the hypoxia-induced stimulation of Epo serves different purposes. Chronologically, the antioxidant effect would most likely come first during the acute phase of hypoxia, while the red blood cell production requires a sustained hypoxic stimulus which stretches beyond the peak of Epo which usually occur within 48 h (Brugniaux & Pichon 2007).