Cloning of hypoxia-inducible factor 1α cDNA from a high hypoxia tolerant mammal—plateau pika (Ochotona curzoniae)

• DOI: 10.1016/j.bbrc.2004.02.087
• Publication Date: 2004-02-27T10:21:49Z
• Authors: T.B. Zhao; H.X. Ning; S.S. Zhu; P. Sun; S.X. Xu; Z.J. Chang; X.Q. Zhao
• Keywords: 0303 health sciences; DNA, Complementary; Base Sequence; Sequence Homology, Amino Acid; Molecular Sequence Data; Lagomorpha; Hypoxia-Inducible Factor 1, alpha Subunit; Adaptation, Physiological; 3. Good health; Mice; 03 medical and health sciences; Animals; Tissue Distribution; Amino Acid Sequence; RNA, Messenger; Cloning, Molecular; Hypoxia; Transcription Factors

Hypoxia-inducible factor 1 is a transcription factor composed of HIF-1alpha and HIF-1beta. It plays an important role in the signal transduction of cell response to hypoxia. Plateau pika (Ochotona curzoniae) is a high hypoxia-tolerant and cold adaptation species living only at 3000-5000 m above sea level on the Qinghai-Tibet Plateau. In this study, HIF-1alpha cDNA of plateau pika was cloned and its expression in various tissues was studied. The results indicated that plateau pika HIF-1alpha cDNA was highly identical to those of the human (82%), bovine (89%), mouse (82%), and Norway rat (77%). The deduced amino acid sequence (822bp) showed 90%, 92%, 86%, and 86% identities with those of the human, bovine, house mouse, and Norway rat, respectively. Northern blot analyses detected two isoforms named pLHIF-1alpha and pSHIF-1alpha. The HIF-1alpha mRNA was highly expressed in the brain and kidney, and much less in the heart, lung, liver, muscle, and spleen, which was quite different from the expression pattern of mouse mRNA. Meanwhile, a new variant of plateau pika HIF-1alpha mRNA was identified by RT-PCR and characterized. The deduced protein, composed of 536 amino acids, lacks a part of the oxygen-dependent degradation domain (ODD), both transactivation domains (TADs), and the nuclear localization signal motif (NLS). Our results suggest that HIF-1alpha may play an important role in the pika's adaptation to hypoxia, especially in brain and kidney, and pika HIF-1alpha function pattern may be different from that of mouse HIF-1alpha. Furthermore, for the high ratio of HIF-1alpha homology among the animals, the HIF-1alpha gene may be a good phylogenetic performer in recovering the true phylogenetic relationships among taxa.