3.2.2. HIF and the Detection of Oxygen in the Environment

As mentioned above, in most mammalian tissues there is between 2% and 9% O2 (an average of 40 mm Hg). In this sense, hypoxia is usually defined as ≤2% O2, whereas severe hypoxia (or anoxia) is defined as ≤0.02% O2 [77]. Therefore, it is important to have mechanisms that detect pO2 in real time to allow the cell to respond appropriately. The change in oxygenation is sensed by HIF (hypoxia-inducible factor), a transfer factor that in hypoxic conditions induces the change from aerobiosis to anaerobiosis. This, in turn, brings about a cascade of events such as the overexpression and activation of enzymes like lactate dehydrogenase (LDH), which is necessary for lactate formation and, simultaneously, activating pyruvate dehydrogenase kinase (PDHK) to prevent pyruvate production [58].

Apparently, the mechanism mediated by HIF and related proteins is highly conserved in animals, making it possible to detect cnidarians and sponges even in basal groups of metazoans [78]. In its active form, HIF is a heterodimer consisting of HIF-1α and HIF-1β. In the case of parasitic flatworms, it is expected that, due to their exposure to different concentrations of O2, during their life cycles, HIF plays a relevant role. In fact, the HIF-1α and HIF-1β proteins have already been characterized in the parasitic nematode *A. suum* [79]. However, it was not until 2019 that a HIF-1α homologue (as well as other associated genes) could be isolated and characterized in the trematode *C. sinensis* (CsHIF-1α) [80]. As expected, CsHIF-1α was highly induced in adults under hypoxic conditions in vitro. Interestingly, CsHIF-1α was sensitive to changes in nitrite and nitric oxide, hence, the authors suggest that these molecules, together with O2, participate in the induction of the response to hypoxia in this organism.
