Zhao T B, Ning H X, Zhu S S, Sun P, Xu S X, Chang Z J, Zhao X Q
Department of Biological Sciences and Biotechnology, Tsinghua Institute of Genome Research, Tsinghua University, Beijing 100084, PR China.
Biochem Biophys Res Commun. 2004 Apr 2;316(2):565-72. doi: 10.1016/j.bbrc.2004.02.087.
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.
缺氧诱导因子1是一种由HIF-1α和HIF-1β组成的转录因子。它在细胞对缺氧反应的信号转导中起重要作用。高原鼠兔（高原鼠兔）是一种高度耐缺氧且适应寒冷的物种，仅生活在青藏高原海拔3000 - 5000米处。在本研究中，克隆了高原鼠兔的HIF-1α cDNA，并研究了其在各种组织中的表达。结果表明，高原鼠兔HIF-1α cDNA与人（82%）、牛（89%）、小鼠（82%）和挪威大鼠（77%）的HIF-1α cDNA高度同源。推导的氨基酸序列（822bp）与人、牛、家鼠和挪威大鼠的氨基酸序列分别具有90%、92%、86%和86%的同源性。Northern印迹分析检测到两种亚型，命名为pLHIF-1α和pSHIF-1α。HIF-1α mRNA在脑和肾中高表达，而在心脏、肺、肝、肌肉和脾中表达较少，这与小鼠mRNA的表达模式有很大不同。同时，通过RT-PCR鉴定并表征了高原鼠兔HIF-1α mRNA的一个新变体。推导的蛋白质由536个氨基酸组成，缺少部分氧依赖性降解结构域（ODD）、两个反式激活结构域（TADs）和核定位信号基序（NLS）。我们的结果表明，HIF-1α可能在鼠兔对缺氧的适应中起重要作用，特别是在脑和肾中，并且鼠兔HIF-1α的功能模式可能与小鼠HIF-1α不同。此外，由于动物之间HIF-1α同源性比例较高，HIF-1α基因可能是恢复分类群之间真实系统发育关系的良好系统发育指标。
