Hypoxia-inducible factor 1 proteomics and diving adaptations in ringed seal

The putative amino acid sequence of ringed seal (Phoca hispida) hypoxia-inducible factor la (HIF-1 alpha) derived from DNA sequence analysis of the single-copy gene has been investigated. The rationale for these studies was to determine the reasons for the presence of HIF-1 alpha at relatively high levels in seal tissues, and its possible role in protection against diving-related oxidative damage. Sequence analysis indicated that the bHLH/PAS and TAD functional domains are very similar to those in terrestrial mammals, although there were significant sequence differences between the mouse and seal proteins in a region of the ODD domain. Some of these results indicate that seal HIF-1 alpha protein can bind HIF-I beta, DNA, transcriptional coactivators, and von Hippel-Lindau protein (pVHL). The presence of HIF-1 alpha in seat tissues was not related to the absence of pVHL, which was found to be present in all seal tissues examined. It is concluded that seal HIF-1 alpha may act as a transcriptional activator and that its presence in seal tissues is probably not caused by its inability to interact with pVHL. It is suggested that seal HIF-1 may serve two functions in the postdiving period, namely, to attenuate ischemia/reperfusion-induced oxidative stress and to allow efficient lung reinflation. (C) 2005 Elsevier Inc. All rights reserved.