Aquatic surface respiration improves survival during hypoxia in zebrafish (Danio rerio) lacking hypoxia-inducible factor 1-alpha

Hypoxia-inducible factor 1-alpha (Hif-1 alpha), an important transcription factor regulating cellular responses to reductions in O-2, previously was shown to improve hypoxia tolerance in zebrafish (Danio rerio). Here, we examined the contribution of Hif-1 alpha to hypoxic survival, focusing on the benefit of aquatic surface respiration (ASR). Wild-type and Hif-1 alpha knockout lines of adult zebrafish were exposed to two levels (moderate or severe) of intermittent hypoxia. Survival was significantly compromised in Hif-1 alpha knockout zebrafish prevented from accessing the surface during severe (16 mmHg) but not moderate (23 mmHg) hypoxia. When allowed access to the surface in severe hypoxia, survival times did not differ between wild-type and Hif-1 alpha knockouts. Performing ASR mitigated the negative effects of the loss of Hif-1 alpha with the knockouts initiating ASR at a higher PO2 threshold and performing ASR for longer than wild-types. The loss of Hif-1 alpha had little impact on survival in fish between 1 and 5 days post-fertilization, but as the larvae aged, their reliance on Hif-1 alpha increased. Similar to adult fish, ASR compensated for the loss of Hif-1 alpha on survival. Together, these results demonstrate that age, hypoxia severity and, in particular, the ability to perform ASR significantly modulate the impact of Hif-1 alpha on survival in hypoxic zebrafish.